Over ten years ago, cdk6 was identified as a new member in a family of vertebrate cdc-2 related kinases. This novel kinase was found to partner with the D-type cyclins and to possess pRb kinase activity in vitro. Recently, several independent studies in multiple cell types have indicated a novel role for cdk6 in differentiation. Since exit from the cell cycle is a necessary step in the process of differentiation, it may not seem surprising that downregulation of a mitogenic factor may be required for this process. It is, however, surprising that this association has not been previously uncovered and that it is apparently not shared with cdk4, long understood to be a functional homolog of cdk6. As this story unfolds it will be important to discover if the role of cdk6 in differentiation is pRb-dependent or pRb-independent, since pRb has long been established as a key factor in initiating and maintaining cell cycle exit during differentiation.