Every organism must have cells that can replicate indefinitely. Can the draft human genome sequence tell us how the cell cycle works and how it evolved? We studied two protein families-the cyclins and their partners the cyclin-dependent kinases (Cdks)-and a conserved regulatory circuit, the spindle checkpoint. Disappointingly, we discovered a few novel cyclins and no new Cdks or components of the spindle checkpoint, and could shed little light on the organization of the cell cycle.