Blood pressure (BP) lowering is one of the most effective interventions to reduce cardiovascular risk. Very recent data from a global BP screening campaign including more than 1.5 million people from 89 countries in whom three standardized BP readings were obtained revealed that hypertension, defined as BP more than 140/90 mmHg or prescription of antihypertensive therapy, was evident in 33.4% of adults screened thereby highlighting the global scale of this problem [1]. If lifestyle interventions fail to control BP pharmacologic antihypertensive therapy is indicated and widely used across the globe. Among the drug classes available, diuretics are generally considered as a first-line choice and widely prescribed either in combination or as mono-therapy [2]. Given the high prevalence of hypertension across the world and the large number of patients prescribed antihypertensive therapy, any major safety concern with a first-line drug class could have important implications. In this context, a number of observational studies over the last few years investigated a possible link between use of diuretics and the risk of various forms of skin cancer. Although there is no evidence to suggest that diuretics and in particular hydrochlorothiazide per se are causing skin cancer, they have inherent photosensitizing activity thereby potentially enhancing the detrimental effects of sun light exposure on the development of various skin cancers. Indeed, hydrochlorothiazide use has previously been reported in some studies to be associated with higher rates of lip cancer and nonmelanoma skin cancers, particularly squamous cell carcinoma [3,4]. Similar findings were reported in a meta-analysis of nine observational studies in which the use of thiazide diuretics was associated with an increased risk of squamous cell carcinoma [adjusted odds ratio (aOR), 1.86; 95% confidence interval (CI), 1.23–2.80] and marginally increased risk of basal cell carcinoma (aOR, 1.19; 95% CI, 1.02–1.38) [5]. In contrast, another meta-analysis of 19 independent observational studies investigating the link between various antihypertensive drugs and skin cancer suggested that calcium channel blocker users were at increased skin cancer risk [summary relative risk (SRR) 1.14, 95% CI 1.07–1.21], and β-blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21, 95% CI 1.05–1.40) with acceptable between-studies heterogeneity (I2 < 50%). No association was found between thiazide diuretics, angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers use and skin cancer risk and there was no evidence of publication bias affecting the results [6]. Although findings from various meta-analysis are conflicting, the British Medicines and Healthcare products Regulatory Agency (MHRA) issued a drug safety update [7] with the recommendation to advise patients taking hydrochlorothiazide-containing products of the cumulative, dose-dependent risk of nonmelanoma skin cancer, particularly in long-term use, and the need to regularly check for (and report) any suspicious skin lesions or moles, to counsel patients to limit exposure to sunlight and ultraviolet (UV) rays and to use adequate sun protection. More recently and potentially more concerning was a research report form Pottegård et al.[8] in which the authors found that patients using hydrochlorothiazide had 22% higher odds of melanoma compared with nonhydrochlorothiazide users. To evaluate potential confounding by indication, the authors performed additional analyses showing that there was no significant association between the risk of melanoma and other BP-lowering medication. Data were obtained from the Danish Cancer Registry in which patients with histologically confirmed melanoma were matched 1 : 10 to cancer free populations. Other relevant information including sun exposure, skin pigmentation, and family history of melanoma were unfortunately not collected and limit the interpretability of the findings [8]. In support of these findings is a small meta-analysis of nine observational studies in which the use of thiazide diuretics was associated with a marginally increased risk of malignant melanoma (aOR, 1.14; 95% CI, 1.01–1.29) [5]. In contrast, Gandini et al.[6] in their meta-analysis of 19 observational studies found no association between the use of thiazide diuretics and cutaneous melanoma. In the current volume of the Journal, Kreutz et al.[9] in a narrative review scrutinize the evidence for such a link and explore potential underlying mechanisms with a specific focus on the photosensitizing effects of diuretics. The widespread use of diuretics for hypertension treatment and other indications such as heart failure renders this a relevant question from a public health perspective. Kreutz et al. analyzed data from a relatively small number of 13 observational studies identified in a literature search restricted to Pubmed and assessing the association between the use of different thiazide or thiazide-like diuretics and risk of several skin cancer types. The selected studies were predominantly from Northern Europe [Denmark (n = 7) other European countries (n = 3)] and the United States (n = 3). Most studies applied a case–control design (n = 9), while others used a cohort design (n = 4). Of the six studies that assessed the association between the use of hydrochlorothiazide and the risk of skin cancer two showed a positive association with malignant melanoma (17 and 32% increased risk), two with squamous cell carcinoma (58 and 75% increased risk), and two with lip cancer (110 and 119% increased risk). Moreover, one study showed a positive association with basal cell carcinoma (8% increased risk), while another did not. Finally, one study showed no association with Merkel cell carcinoma or malignant adnexal skin tumors overall but a positive association with high cumulative dose. Three studies looked specifically at the association between the use of indapamide or other thiazide-like diuretics and the risk of skin cancer. Of those, two showed a positive association with malignant melanoma (49 and 230% increased risk) and no association with either basal cell or squamous cell carcinoma, neither overall nor with high cumulative dose. Aside from reviewing the evidence available from observational studies, the authors also reviewed the basic mechanisms of drug-induced photosensitivity and highlight that not only diuretics, but in fact most other commonly used antihypertensive drugs have photosensitizing capacity, possibly explaining some of the heterogeneity seen between various meta-analysis mentioned above. The authors also make an important point highlighting that drug-induced photosensitivity reactions are a function of the inherent photosensitizing activity of the individual drug, the amount of radiant energy, and drug concentration in the skin. Hence, unavailability of these relevant data will make it difficult to interpret the data appropriately. Where to go from here and what are the implications of these recent findings for practicing physicians and patients under their care? There are a few important isssues that need to be taken into account and require further investigations. Importantly, all studies evaluated in the review by Kreutz et al.[9] and other meta-analyses [5,6] are of observational nature and have important methodological issues that render the interpretation of their findings difficult as outlined appropriately in the review. These data are therefore insufficient to guide any changes from currently well established prescribing practices in regards to antihypertensive therapies, in particular the use of thiazide and thiazide-like diuretics for the treatment of hypertension and other conditions as recommended by recent international guidelines [2]. Intriguingly, available pharmacological evidence shows that photosensitivity is not a unique feature of thiazide diuretics such as hydrochlorothiazide but should also be expected among thiazide-like or other diuretics and antihypertensive drugs. It will therefore indeed be important that well conducted observational studies are being initiated to provide more solid evidence on the possible association between the use of thiazide or thiazide-like diuretics as well as other antihypertensive drugs and the risk of skin cancer. This does not mean that signals from these studies should be ignored, but any response has to be measured and take into account the benefit-to-risk ratio. The guidance provided in that regard by the MHRA in their drug safety update [7] recommending regularly checks for any suspicious skin lesions or moles and to counsel patients to limit exposure to sunlight and UV rays and to use adequate sun protection if using these types of drugs seem appropriate until further evidence becomes available. At this stage, there is clearly no reason to withdraw diuretics from the antihypertensive regimen of individual patients but provide them with relevant imformation pertaining to the potential risk of skin cancers and appropraite protective measures. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.