An estimated 500,000 laboratory workers in the United States are at risk of exposure to infectious agents that cause disease ranging from inapparent to life-threatening infections, but the precise risk to a given worker unknown. The emergence of human immunodeficiency virus and hantavirus, the continuing problem of hepatitis B virus, and the reemergence of Mycobacterium tuberculosis have renewed interest in biosafety for the employees of laboratories and health care facilities. This review examines the history, the causes, and the methods for prevention of laboratory-associated infections. The initial step in a biosafety program is the assessment of risk to the employee. Risk assessment guidelines include the pathogenicity of the infectious agent, the method of transmission, worker-related risk factors, the source and route of infection, and the design of the laboratory facility. Strategies for the prevention and management of laboratory-associated infections are based on the containment of the infectious agent by physical separation from the laboratory worker and the environment, employee education about the occupational risks, and availability of an employee health program. Adherence to the biosafety guidelines mandated or proposed by various governmental and accrediting agencies reduces the risk of an occupational exposure to infectious agents handled in the workplace.