Over the past several years, a number of human tumor suppressor genes have been cloned and characterized. Germline mutations in tumor suppressor genes strongly predispose to cancer, and they are also mutated somatically in sporadic forms of the disease. In order to create animal models for the familial cancer syndromes caused by inherited mutations in these genes as well as to determine their role in embryogenesis, the homologues of several members of this class have been mutated in the mouse. The initial characterization of the heterozygous and homozygous phenotypes caused by these mutations has led to important insights into the mechanisms by which tumor suppressor genes participate in normal development and how their loss contributes to tumorigenesis.