The incidence of non-Hodgkin's lymphoma (NHL) has increased approximately 80% since the 1970s, and is now the fifth most common cancer in the United States. The incidence of NHL is approximately 50% higher among men than women and 35% higher among white people than black people. The incidence rates of all subtypes of NHL have increased, especially diffuse large-cell and immunoblastic subtypes. Extranodal NHL has increased more rapidly than nodal NHL. The overall NHL incidence rates stabilized in the early 1990s and then began to decrease between 1996 and 2000, resulting in part from a decrease in the incidence of AIDS. The incidence of NHL types not associated with AIDS and NHL in groups at low risk of AIDS has continued to increase throughout the 1990s. The increasing incidence of NHL is poorly understood. Improved diagnostic techniques, the effects of the human immunodeficiency virus epidemic, and immunosuppressive therapies accounted for only one third of the increase. Increase in NHL may be attributed to immunodeficiency, various infections, familial aggregation, blood transfusion, genetic susceptibility to NHL, diet, and chemical exposures to pesticides and solvents. Some studies also suggest that associations between risk factors and specific NHL subtypes may be stronger than associations between the same risk factors and NHL in aggregate. Future epidemiologic studies should incorporate the new World Health Organization classification of NHL and new techniques such as cytogenetic molecular analyses to identify subtype-specific etiologic factors. Evaluation of polymorphisms in genes involved in immune function, inflammation, and the activation or detoxification of environmental and occupational chemicals is also warranted.