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Laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. Although the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that Brucella species, Shigella species, Salmonella species, Mycobacterium tuberculosis, and Neisseria meningitidis are the most common causes. Infections due to the bloodborne pathogens (hepatitis B virus, hepatitis C virus, and human immunodeficiency virus) remain the most common reported viral infections, whereas the dimorphic fungi are responsible for the greatest number of fungal infections. Because of the increasing attention on the role of the laboratory in bioterrorism preparation, I discuss the risk of laboratory-acquired infection with uncommon agents, such as Francisella tularensis and Bacillus anthracis. Physicians who care for a sick laboratory worker need to consider the likelihood of an occupationally acquired infection while advising exposed laboratory workers about postexposure prophylaxis. In addition, physicians should be aware of the importance of alerting the laboratory if infection with a high-risk agent is suspected.