Understanding of cyclin-dependent kinase (CDK) regulation in mammalian cells has deepened even as the functions ascribed to these enzymes have multiplied. We know from crystallographic studies how a prototypic CDK-cyclin complex is activated and inactivated; the challenge now is to extend this knowledge to other CDKs involved in cell cycle progression. At the same time, as CDKs turn up in some unexpected places, interest in CDK regulation has spread beyond the cell cycle field.