Occupational exposures to blood-borne pathogens occur regularly in diverse settings and involve multiple groups of healthcare workers. Current compliance of healthcare workers with behavioral controls is poor, and additional engineering and work-practice controls for exposure prevention are inadequate and/or underutilized. Barriers to effective postexposure management include deficient knowledge and fear and denial among healthcare workers, the diverse risks associated with different exposures, the costs and personnel necessary for providing exposure management 24 hours a day, variable levels of expertise in postexposure prophylaxis strategies, and administrative requirements for standardized policies and procedures. In the current environment, healthcare institutions are largely ill equipped to provide timely and effective postexposure prophylaxis. Widespread worker education, simplified reporting mechanisms, and availability of prompt source and worker testing along with timely, free postexposure prophylaxis is central to an institution's postexposure program. Postexposure management programs should be comprehensive and provide standardized procedures, expand workers' access to postexposure prophylaxis by establishing responsible parties in diverse areas, disseminate program information to all workers, and ensure confidentiality in the care and follow-up of exposed workers. To implement such programs, it may be necessary to merge resources and link local management of exposures with regional expertise to provide up-to-date counseling in a rapidly changing field. Careful surveillance of occupational exposures is essential to evaluate program efficacy, direct prevention efforts, and to determine necessary resources to ensure continued successful delivery of postexposure prophylaxis.