Cells normally respond to DNA damage by activating checkpoints that delay the transition from G1 to S and from G2 to M while DNA is repaired. The checkpoints thus protect cells by blocking replication of damaged DNA and segregation of damaged chromosomes. Most cancer cells have an inoperative G1 checkpoint due to p53 inactivation, and a functioning but impaired G2 checkpoint. Inhibitors of the G2 checkpoint can selectively sensitize cells with inactive p53 to killing by DNA-damaging drugs or ionizing radiation and might be useful in cancer therapy. Cell-based and target-directed screens for checkpoint inhibitors have been developed and several checkpoint inhibitors have been identified. This review describes their chemical structures, biochemical targets and cellular effects and discusses their therapeutic potential.