Health-Care Personnel (HCP) are at increased risk of acquiring occupational infections in the health care setting. A series of prevention strategies can be implemented to reduce the risk of those exposures, but it is agreed that education, training, personal protective equipment, safe procedures and work practices will not prevent all exposures and that there is a need of a number of interventions to further reduce the risk of acquiring an infectious disease after an exposure and in reducing the risk of secondary spread of infection. Postexposure prophylaxis (PEP) could be recommended following exposure to a wide spectrum of viral and bacterial diseases, and might include vaccines, immune globulins, antibiotics, and antiviral medications. All health-care institutions should ensure to have systems in place to facilitate postexposure assessment, and have prophylaxis readily accessible for timely administration. The protocol should describe procedures for the rapid provision of medical care during all work hours (day, evening, and night shifts). Postexposure management approach will depend on the type and extent of exposure, characteristics of the infectious agent (eg, virulence, infectious dose), status of the source patient, the exposed person’s susceptibility to infectious diseases of concern, and the relative risks and benefits of the PEP regimen in each individual situation. Occupational exposures should be considered urgent medical concerns to ensure timely postexposure management. Exposed HCP should be monitored for signs and symptoms of infection and for possible adverse effects from drugs. In the absence of PEP, recommendations for postexposure management are intended to achieve early identification of disease and, if present, referral for evaluation of treatment options. Management of exposures should always be fully documented and exposures reported to the appropriate administrative department. A key administrative component is provision of resources for maintenance of infection control and occupational health programs that are responsive to emerging needs.