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. 1 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 down-regulation 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 a 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.