Progression through the eukaryotic cell cycle is regulated by the activities of a family of cyclin dependent kinases (CDKs). These kinases are negatively regulated by phosphorylation and by the action of cyclin kinase inhibitors (CKIs). In mammalian cells, two classes of CKIs have been identified, the INK4 class and the CIP/KIP class. These CKIs are versatile negative regulators of CDK function and have potential roles in development, checkpoint control and tumour suppression. Analysis of CKI knockout indicates that although these inhibitors are not generally required for survival, the phenotypes observed span the gamut of what might be expected for loss of a cell cycle inhibitor. This chapter summarizes our current understanding of the roles of CKIs in growth control.