In recent years, genes associated with cancer have been studied to assess their possible use as predictive indicators for cancer therapies. Among these, the gene product of the tumor suppressor gene p53 was found to play an important role in cancer therapy. The p53 molecule induces cell-cycle arrest, apoptosis and DNA repair after cells are subjected to cancer therapies involving radiation, heat and various anti-cancer agents. Mutations in p53 are observed at a high frequency in human tumors, and are present in about half of all malignant tumors in humans. Sensitization to radiation, heat and anti-cancer agents was observed in cells containing wild type p53, but not in cells containing mutated p53. This review discusses p53 activation of signaling pathways after exposure to cancer therapies which target p53; such therapies include chemical chaperones, the p53 gene, p53-C terminal peptides, and p53-targeting agents which enhance p53-central signal transduction pathways.