p53 is the most frequently mutated gone in human cancer cells. Its wild-type gone encodes for a protein with pivotal functions: (i) interaction with key players in the cell cycle leading to cell cycle arrest; (ii) induction of programmed call death, or apoptosis. P53 may be seen as another member of the family of proteins involved in resistance to anticancer therapy, since mutations/deletions involving the p53 gene lead frequently to resistance of radiation/cytotoxic drug treatment. Consequently, patients with p53-mutated tumors may harbor a worse prognosis. On the other hand, reintroducing wild-type P53 may lead to an adequate function of the cellular cell cycle and/or apoptosis program, thus enabling efficient anti-cancer therapy even in the presence of mutated P53. Two options are being discussed: (i) gene therapy approaches; (ii) modulating mutated P53 with yet unknown molecules.