CDK1 is activated by binding to its partners cyclin A or cyclin B and requires phosphorylation of Thr161 within the activation segment for full activity.  During mitosis CDK1–cyclin B phosphorylates a large number of substrates to break down the nuclear membrane, separate the sister chromatids and drive the cell through cytokinesis. Together these events generate two daughter cells. We have determined the crystal structures of CDK1–Cks1 and CDK1– cyclin B–Cks2. These structures confirm the conserved nature of the inactive monomeric CDK fold and its ability to be remodelled by cyclin binding. Relative to CDK2–cyclin A, CDK1–cyclin B is less thermally stable, has a smaller interfacial surface, is more susceptible to activation segment dephosphorylation and shows differences in the substrate sequence features that determine activity (see Figure). Ultimately CDK1 activity is lost as its activating cyclin subunits are targeted for degradation via the ubiquitin proteasome system and phosphatases remove the phosphate groups added to proteins by CDK1. The cell now enters G1 and will again prepare to make the decision as to whether to commit to another round of DNA replication and cell division.