Genetic susceptibility to bladder cancer in individuals exposed to arylamines may be explained by interindividual metabolic differences that lead to arylamine bioactivation or detoxification. In this article, occupational bladder cancer risk factors and the evidence that links benzidine exposure to bladder cancer are reviewed. Benzidine metabolism is described and compared with that of other aromatic amines. Metabolic polymorphisms and bladder cancer in the context of occupational exposure to aromatic amines are also reviewed, and the environmental and genetic relationships of benzidine exposure and genetic susceptibility are outlined. Only a few studies of bladder cancer genetic susceptibility in populations exposed occupationally to arylamines have been published. The results of these case-control studies show conflicting results, reflecting metabolic differences between monoarylamines and diarylamines such as benzidine. Additional studies and pooled analyses of existing data are needed to establish if individuals are at higher risk of bladder cancer given the presence of certain alleles that make them more susceptible to this disease.