One of the most productive areas of biologic research has been the utilization of model organisms for the systematic study of gene function. Although the experimental manipulation of these model genetic systems has provided important insights into the function of homologous genes in humans, such studies are necessarily limited by the need to extrapolate among divergent species and cell types. Researchers have now begun to apply the technology of gene targeting to human cell lines. Recently, studies of human cell knockouts have yielded important new information about how the cell cycle is regulated and how this regulation can go awry in cancer cells. The targeting of human genes promises to be a powerful tool in the characterization of the molecular pathways relevant to cancer.