p53 is a key tumor suppressor that plays a critical role in coordinating the response of cells to a diverse range of stress conditions, e.g. oncogenic activation, hypoxia or DNA damage. Induction of cell death by apoptosis in response to stress by p53 is crucial for the prevention of tumor development as well as for the response to anticancer therapy. p53 triggers apoptosis through multiple mechanisms, including mitochondrial and death receptor pathways, cytoskeleton changes, suppression of survival signalling, and induction of hypoxia. Lesions in the p53 pathway occur so frequently in cancer, regardless of patient age or tumor type, that they appear to be part of the life history of a majority of cancer cells. Given an extremely high potency of apoptosis induction by functional p53, it appears that anti-cancer strategies based on p53 reactivation should be efficient and applicable in a wide range of human tumors. Tumor cells are prone to p53-induced apoptosis due to oncogene activation. Therefore it is conceivable that p53-based therapeutic strategies will not require selective targeting of tumor cells.