Acne and rosacea are frequently encountered in the clinical practice of a dermatologist. These diseases can develop simultaneously in the same patient. Most often, the erythematous form of rosacea is combined with acne. Because of the similarity of clinical manifestations with acne, the diagnosis of rosacea can be easily missed. Common pathogenetic factors in the 2 diseases are thought to be genetics, alterations in the microbiome, immune disorders, and skin barrier dysfunction. There are few works addressing the relationship between acne and rosacea. A recent study identified a number of common differentially expressed genes, including interleukin-1B and matrix metalloproteinase 9, and showed that gamma delta T cells may play an important role in the development of both diseases. Despite the common pathogenesis and the similarity of some clinical manifestations (papules and pustules), acne and rosacea must be distinguished. In rosacea, there is persistent facial erythema induced by vasoregulatory neutropeptides, whereas in acne, the inflammatory process is due to excess sebum and changes in the skin microbiome. Isotretinoin is used for systemic therapy of both diseases. The drug affects the level of some cytokines, including inhibiting the expression of matrix metalloproteinase 9. In addition, it reduces sebum production in acne, and due to its ability to alter the skin microenvironment, it can reduce Propionibacterium acnes in acne and Demodex folliculorum in rosacea. Daily and cumulative doses for rosacea and acne will differ, as will topical therapy for these conditions. For acne, the combination of clindamycin and benzoyl peroxide is well established for the treatment of acne, allowing rapid meaningful clinical effect. In rosacea, metronidazole in cream form, which has better tolerability, is recommended as a topical agent. In patients suffering from both diseases simultaneously, a combination of clindamycin and benzoyl peroxide should be used to relieve acute inflammation, after which it is possible to switch to metronidazole.