Worldwide, transgender populations are disproportionately affected by human immunodeficiency virus (HIV). Pervasive stigma and discrimination impact social and economic determinants of health, which perpetuate HIV disparities among transgender individuals. This article reviews the prevalence of HIV infection among transgender populations and presents psychosocial, behavioral, and individual level factors that contribute to HIV acquisition. The authors provide practical recommendations regarding a patient-centered approach to HIV/sexually transmitted infection risk assessment. The role of preexposure prophylaxis utilization in preventing the transmission of HIV is discussed as well as the current data on HIV treatment outcomes for transgender people living with HIV.