p21 and p16, first identified as two small molecular weight proteins in CDK and cyclin immunocomplexes, represent two distinct families constituting a total of seven CDK inhibitors in mammalian cells. The physiological functions of these genes are believed to be broadly involved in connecting various cellular pathways to cell cycle control. Extensive studies over the past 10 years have led to a fairly clear understanding of their biochemical and cellular mechanisms and have also left some unresolved and controversial issues.