Rationale for guideline update Six years after the Southern African HIV Clinicians Society cryptococcal disease guideline was published in 2013, cryptococcal meningitis (CM) remains an important cause of mortality among antiretroviral treatment (ART)-naive and ART-experienced HIV-seropositive adults in South Africa.1,2 Several important practice-changing developments led us to update the guideline to diagnose, prevent and manage this common fungal opportunistic infection. The World Health Organization (WHO) published a guideline for advanced HIV disease in 2017 and a guideline relevant to resource-limited settings for HIV-associated CM in 2018.3,4 Cryptococcal antigen (CrAg) screening and pre-emptive treatment reduced all-cause mortality among ambulatory participants in a randomised clinical trial in Zambia and Uganda.5 Following an evaluation of reflex versus provider-initiated screening, national reflex laboratory CrAg screening was implemented in South Africa in 2016.6,7 Recently completed clinical trials conducted in resource-limited settings have provided evidence for the best first-line antifungal regimens for CM and the role of corticosteroids in CM.8,9 Finally, international and local advocacy efforts have resulted in increasing, yet still limited, access to flucytosine and a reduced cost of liposomal amphotericin B for the treatment of CM.10