The emergency department is where many healthcare workers will seek medical advice and care after a potential exposure to bodily fluids contaminated with the human immunodeficiency virus (HIV). The estimated risk of HIV infection in healthcare workers with percutaneous exposures to HIV-infected blood is estimated at 0.3% to 0.32%. Zidovudine (AZT) post-exposure prophylaxis has been associated with a 79% reduction in the risk of seroconversion in a case-control study sponsored by the Center for Disease Control and Prevention (CDC), and has become part of the standard prophylactic treatment for patients with occupational HIV exposure. This article reviews the current CDC recommendations as well as our institutional practice guidelines for the management of healthcare workers who are exposed to potential or confirmed HIV-infected fluids.