Pharmacogenomics is the study of inherited differences in interindividual drug disposition and effects. A major goal of this effort in cancer chemotherapy is the avoidance of severe, potentially life-threatening drug toxicity for patients. Genetic polymorphisms in drug-metabolizing enzymes and other molecules involved in drug disposition are responsible for much of the interindividual differences in the toxicity of many chemotherapy agents. This review will discuss clinically relevant examples of gene polymorphisms that influence toxicity and the experimental tools that have been utilized for discovering toxicity-related polymorphisms.