Agents that induce DNA damage in cells--the so-called genotoxins--have successfully been used for decades to treat patients with tumors. Genotoxins alter the DNA of cells, which is detected by DNA damage sensors and which leads to the activation of p53. Activation of p53 can lead to the death of cancer cells. The efficacy of genotoxins in humans is however limited by their toxicity to normal tissues. Specific sensitization of tumor cells to the action of genotoxins would reduce the efficacious doses of genotoxins to be used in patients, diminishing the detrimental side-effects of the drugs on normal tissues. A series of compounds able to sensitize cancer cells to DNA-damaging drugs have recently been identified that have the potential to increase the efficacy of currently used anti-cancer treatments.