Renal cell cancer accounts for about 2% of cancers worldwide. It has been increasing in incidence in North America and northern Europe, but not in other areas of the world. In the United States the rate of increase has been about 3% per year, with the highest rates now seen among blacks. Survival has improved, with the 5-year relative survival rate increasing from 30% to 40% in the 1960s to between 50% and 60% in the 1990s. A large number of epidemiologic studies, particularly case-control investigations, have searched for clues to the etiology. Cigarette smoking is a causal factor in the development of renal cell cancer. Virtually every study has identified obesity or high relative weight as another major determinant, particularly among women. High blood pressure or its medications may also play a role, although the mechanism is unknown. Occupational exposures such as asbestos, coke oven emissions, gasoline, and solvents have been related to an excess risk, but no convincing evidence exists regarding these or any other occupational factor. An inverse association between risk and intake of fruits and vegetables has been seen in a number of studies and remains one of the few consistent dietary findings. A relation with coffee, alcohol, or any other beverage has not been demonstrated for renal cell cancer and is unlikely to exist. Genetic susceptibility plays a significant role in an unknown portion of cases, likely through a number of mechanisms. Future etiologic studies should focus on the mechanism by which obesity increases risk, the role of high blood pressure and its medications, and the reasons for the remarkedly rapid increase in incidence among blacks in the United States.