There is a low risk of infection with the human immunodeficiency virus (HIV) for HCW through exposure in the work place. The mean risk of infection with HIV after a percutaneous exposure is 0.3%. This risk can be considerably higher depending on various factors: for example, a deep percutaneous injury or the source patient being in an end stage of HIV infection. Despite compliance with adequate precautions, it is not always possible for HCW to avoid injuries. This fact has made intervention desirable after such exposure. Zidovudine (AZT) was available as the first effective drug for treatment of HIV infection. Also, animal experiments have shown efficacy in prophylactic use of zidovudine. Therefore, since the beginning of the 90's, there has been an increased use of postexposure prophylaxis with zidovudine for exposed HCW, and during this period of use more evidence has come up to show the efficacy of PEP. In fact, a large retrospective case-control study showed a 81% reduction of HIV transmission to exposed HCW in the zidovudine treated group after percutaneous exposure. Based upon this impressive evidence and other data which indicate the efficacy of PEP, postexposure prophylaxis has become a standard procedure in the health care setting after a significant exposure to HIV. A combination of three antiretroviral drugs, usually including a protease inhibitor, is used today. Based on our current pathogenetic understanding, PEP should be started as soon as possible after exposure to HIV. There are effective tools for preventing HIV transmission in the general population. However, these tools do not provide universal protection: rupture of condoms, needle sharing and unprotected intercourse with a HIV infected person are situations at risk of HIV transmission. In spite of a different mode of exposure when compared to the health care setting, PEP in timely application is believed to be efficacious. To date there is no controlled data to support PEP in such situations; however, PEP with a combination of antiretroviral drugs after anal, oral (with ejaculation) or vaginal intercourse and needle sharing with a HIV-positive partner is recommended for a minimum of two weeks. There are reservations in recommending PEP after unprotected sexual intercourse with a partner of unknown serostatus.