The development of cancer requires multiple genetic alterations perturbing distinct cellular pathways. In human cancers, these alterations often arise owing to mutations in tumor-suppressor genes whose normal function is to either inhibit the proliferation, apoptosis, or differentiation of cells, or maintain their genomic integrity. Mouse models for tumor suppressors frequently provide definitive evidence for the antitumorigenic functions of these genes. In addition, animal models permit the identification of previously unsuspected roles of these genes in development and differentiation. The availability of null and tissue-specific mouse mutants for tumor-suppressor genes has greatly facilitated our understanding of the mechanisms leading to cancer. In this review, we describe mouse models for tumor-suppressor genes.