Occupational exposures to the human immunodeficiency virus (HIV) continue to occur in the health care setting. Each such exposure is associated with risk for occupational infection. Although occupational HIV infections have been uncommon in health care workers, the occurrence of even one such infection is traumatic for the health care worker and his or her institution. To attempt to prevent infection following occupational exposures, some institutions and investigators have elected to offer postexposure chemoprophylaxis with zidovudine. Unfortunately, data describing the use of nucleoside analogues in animals and humans as antiviral chemoprophylaxis are quite limited and data simply do not exist that definitively support or refute their use in this setting. One can mount an equally reasonable argument for or against the use of these agents in this setting in 1990. This article reviews the available data regarding postexposure chemoprophylaxis, summarizes the clinical experience with zidovudine use for postexposure chemoprophylaxis to date, and evaluates prospects for additional chemoprophylaxis options in the future.