Occupational disease is responsible each year in the United States for 50,000 to 70,000 deaths and for approximately 350,000 new cases of illness. Occupational diseases affect all organ systems and include pulmonary disease, musculoskeletal injuries, occupational cancer, traumatic injuries, occupationally induced cardiovascular disease, disorders of reproduction, neurotoxic disorders, noise-induced hearing loss, dermatologic conditions, and psychological disorders. Occupational diseases may be very difficult to diagnose. Pathognomonic signs and symptoms are rare; most occupational diseases are clinically indistinguishable from disease of other etiologies. Diagnosis is complicated further by the long latency typical between a toxic occupational exposure and the appearance of illness. Further, there is widespread lack of information on the toxicity of most chemical substances in use in American workplaces, and workers frequently are not informed of the nature or the hazards of the materials with which they work. The occupational history is the principal clinical instrument for the diagnosis of occupational disease. All patients should undergo at least a brief occupational history that inquires about the current job, including both industry and occupation, the longest-held previous jobs, and any toxic occupational exposures to chemicals, fumes, gases, dust, noise, or radiation. Proper diagnosis of occupational disease permits proper treatment of the affected patient and also provides a basis for recognition of other similarly employed persons who may also be at risk of toxic exposure. Occupational diseases are highly preventable. Prevention is most efficiently achieved by removing hazardous materials from the workplace and replacing them with less hazardous substances. Other approaches to prevention include ventilation, alteration in work practices, and use of personal protective equipment. Physicians in the United States are for the most part not well trained to recognize occupational illness. At the same time, there is a great lack of qualified specialists in occupational medicine. The majority of care of patients with occupational disease will therefore continue to be the responsibility of primary care physicians, and these physicians must become more highly attuned to the possibility that their patients may have diseases induced by toxic exposures encountered at work. The development of a heightened sensitivity of primary care providers to occupationally induced disease is an urgent priority.