Objective: Cryptococcal meningitis is one of the most important HIV-related opportunistic infections, especially in the developing world. In order to help develop global strategies and priorities for prevention and treatment, it is important to estimate the burden of cryptococcal meningitis. Design: Global burden of disease estimation using published studies. Methods: We used the median incidence rate of available studies in a geographic region to estimate the region-specific cryptococcal meningitis incidence; this was multiplied by the 2007 United Nations Programme on HIV/AIDS HIV population estimate for each region to estimate cryptococcal meningitis cases. To estimate deaths, we assumed a 9% 3-month case-fatality rate among high-income regions, a 55% rate among low-income and middle-income regions, and a 70% rate in sub-Saharan Africa, based on studies published in these areas and expert opinion. Results: Published incidence ranged from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2%, 720000 cases; range, 144000-1.3 million). Median incidence was lowest in Western and Central Europe and Oceania (≤0.1% each). Globally, approximately 957 900 cases (range, 371 700-1 544 000) of cryptococcal meningitis occur each year, resulting in 624700 deaths (range, 125000-1 124900) by 3 months after infection. Conclusion: This study, the first attempt to estimate the global burden of cryptococcal meningitis, finds the number of cases and deaths to be very high, with most occurring in sub-Saharan Africa. Further work is needed to better define the scope of the problem and track the epidemiology of this infection, in order to prioritize prevention, diagnosis, and treatment strategies. © 2009 Wolters Kluwer Health|Lippincott Williams & Wilkins.