The viral biology, immunologic and clinical manifestations, and strategies for effective control of HIV infection have been extensively elucidated. Dozens of antiviral drugs (ARVs) are available to target various stages of the viral life cycle. These drugs and other measures have drastically reduced the global burden of HIV/AIDS. However, the genome, structure, and molecular machinery the virus possesses to facilitate its dissemination equip it with a remarkable array of immunoevasive properties that hinder the development of prophylactic and therapeutic vaccines. With ARVs as the only effective treatment, ongoing efforts focus on (1) refined diagnostic testing that facilitates early linkage to care, (2) effective non-pharmaceutical prevention techniques (e.g., condom use and male circumcision), (3) novel classes (e.g., injectable) of ARVs for preexposure prophylaxis and for simplified, long-term therapeutic regimens, (4) management of comorbidities associated with premature aging and impaired immunologic health, and (5) the possibility of a functional cure of HIV infection that would hasten the end of AIDS. However, success at control and prevention has been highly variable from country to country, and the lack of concerted allocation of resources for sustained and comprehensive patient care can falter under geopolitical uncertainties. To date, few countries have succeeded in reaching the World Health Organization 2025 milestones for population knowledge of HIV status, receipt of treatment, and sustained viral suppression. Although it also remains to be seen if the pursuit of other more ambitious goals like functional cure will unravel in the future, hopefully the momentum gained from decades of progress can be sustained.