After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.