Tumour cells grow and divide in an uncontrolled fashion. Recent advances in the cell cycle have uncovered new mechanisms that integrate growth and division with chromatin and gene expression control. Small-molecule drugs that target key enzyme classes involved in these pathways, the cyclin-dependent kinases (Cdk) in the cell cycle and histone deacetylases (HDAC) in chromatin control, have entered clinical studies, with emerging clinical efficacy. These new mechanism-based approaches could provide significant improvements over many current chemotherapeutics.