The cellular response to the stress induced by treatment with anticancer agents is a key determinant of drug activity. A pivotal role in this response is played by checkpoint proteins that control the normal passage of cells through the cell cycle. There is evidence that cancer cells often have defects in one checkpoint control that makes them more vulnerable to inhibition of a second checkpoint, thereby enhancing the overall response to treatment. The G1 and G2 checkpoints are particularly crucial for the decision of a cell to arrest in the cell cycle after damage. The checkpoints are used to try to allow the repair of any damage, or to activate the apoptotic (programmed cell death) machinery. Inhibition of both G1 and G2 checkpoints in cancer cells is therefore likely to result in an induction of the death response in cancer cells. Similarly, an increasing knowledge of the molecular mechanisms that form the basis of apoptotic pathways has helped to define why cancer cells have a reduced propensity to undergo apoptosis following the activation of apoptotic inhibitory pathways or the inhibition of pro-apoptotic pathways. Therefore, the possibility to modulate these pathways is likely to result not only in the increased activity of anticancer agents, but also in an increase in their specificity.