Cyclin-dependent kinase 2 (CDK2) regulates diverse aspects of the mammalian cell cycle. Most cancer cells contain mutations in the pathways that control CDK2, and CDK2 activity has received much attention as a target for cancer therapy. However, a recent report demonstrating that some cancer cells can proliferate without CDK2 activity questions the essential role of CDK2 in cell-cycle control, as well as its suitability as a therapeutic target.