This report updates previous US Public Health Service recommendations for the management of health-care personnel (HCP) who experience occupational exposure to blood and/or other body fluids that might contain human immunodeficiency virus (HIV). Although the principles of exposure management have not changed, recommended HIV postexposure prophylaxis (PEP) regimens and the duration of HIV follow-up testing for exposed personnel have been updated. This report emphasizes the importance of primary prevention strategies, prompt reporting, adherence to HIV PEP regimens, expert consultation, follow-up of exposed HCP to improve adherence to PEP, and careful monitoring for adverse events. The report outlines several special circumstances including delayed exposure report, unknown source person, pregnancy in the exposed person, resistance of the source virus to antiretroviral agents, or toxicity of the PEP regimen when other consultation is advised.