HIV infection continues to pose a critical risk to health in many countries. UNAIDS estimates that as of 2016 the total HIV-infected population was 36.7 million, including 1.8 million people newly infected that year. Although some 19.5 million people are receiving antiretroviral treatment, a substantial treatment gap leaves many millions of people at risk of AIDS-related diseases and, if unaware of their status, likely to infect others. Research is seeking new approaches to prevent, treat, and ultimately cure HIV infection. This PLOS Special Issue features a selection of resources looking at these advances.