The uneven distribution of HIV risks and burdens across populations is a well-substantiated fact, though seldom publicly acknowledged. Gay men and other men who have sex with men, people who inject drugs, sex workers, and transgender women are 24, 24, 13.5, and 49 times more likely to acquire HIV, respectively, than other reproductive aged adults (15 years old and older). Globally, new infections among these key populations account for 45% of all new HIV infections. This figure is likely to be an underestimate, given the intense stigma associated with disclosing and reporting acquisition risks for HIV among gay men, people who use drugs, sex workers, and transgender people. In addition, HIV epidemics in the majority of low- and middle-income countries (90 of 120) have concentrated epidemics among key populations. In countries with more broadly generalized epidemics, risks are still not evenly distributed and key populations still shoulder disease burden that is markedly disproportionate.