Recent research has yielded a dramatic increase in the number of connections between oncogenesis and the proteins which regulate the cell cycle. Three classes of protein which inhibit the activity of cyclin-dependent kinases (CDKs) have emerged as potential targets for oncogenic inactivation. p16 and related proteins inhibit the cyclin/CDK complexes which regulate the transition from G1 to S phase; numerous studies have revealed that p16 is mutated in most tumor cell lines and in some types of primary tumor. p21/WAF1/Cip 1 and the related p27Kip protein inhibit a broader range of cyclin/CDK complexes than p16. Although the absence of p21/WAF1/Cip1 from cyclin/CDK complexes is correlated with cellular transformation, no mutations in this gene have been found in tumors or tumor-derived cell lines. A third class of genes which are potential targets for oncogenic inactivation are the kinases and phosphatases which regulate the activity of cyclin/CDK complexes by phosphorylation and dephosphorylation of the CDK proteins. Disruption of any of these genes would result in loss of normal regulation of cell growth.