Use of antiretroviral drugs to reduce the risk of HIV infection following exposure to the virus is now widespread. Although there are no randomized controlled trials, there are limited data supporting the effectiveness of post-exposure prophylaxis (PEP). The decision to prescribe PEP follows risk assessment by an appropriately trained doctor. Occupational exposure from an infected patient is more likely to cause infection with blood transmission, when the injury is deep and when blood is visible on the device. Different types of sexual exposure carry different risks of infection; receptive anal intercourse carries the most, followed by vaginal intercourse; receptive oral sex is not risk free. Whenever possible, a source of unknown HIV status should be given appropriate counselling and tested; alternatively the probability of a source being infected may be estimated from their social group. The final decision regarding PEP should be made individually, taking into account the risk of the exposure, the potential long-term and short-term side-effects of drug treatment and the wishes of the individual. It is recommended to begin PEP within 1 hour of exposure, and it may therefore be necessary to begin treatment while awaiting a formal risk assessment. It is important that starter packs of PEP are available in appropriate areas such as A&E departments, occupational health departments and pharmacies. Further management should be coordinated by a physician experienced in HIV care. PEP following sexual exposure is usually prescribed only by genitourinary medicine clinics and is recommended only within 72 hours of exposure.