Universal precautions are work practices designed to protect health care workers from occupational exposure to HIV and other bloodborne pathogens. However, despite aggressive dissemination efforts by CDC and regulatory action by OSHA, compliance remains less than satisfactory. This article argues that the minimization of risk from bloodborne pathogens requires a multilevel or work-systems perspective that considers individual, job/task, and environmental/organizational factors. The available literature on universal precautions suggests the potential of such an approach and provides insight into the limited success of current worker-focused mitigation efforts. In particular, specific opportunities exist to develop and apply engineering controls, to improve the design and organization of jobs and tasks, and to create organizations that facilitate and reinforce safe behavior.