This chapter summarizes what has been learned about TP53 in cancer. It focuses on the cellular mechanisms of TP53 activity. The chapter analyzes the mechanisms of TP53 inactivation in tumors and the consequences of TP53 inactivation on tumor cell phenotype. It also focuses on the role of TP53 in the organism and, overview potential clinical applications that have stemmed from TP53 research. The TP53 protein is the subject of complex post-translational modifications and regulation. The description of the mechanisms of TP53 protein activation and function is one of the main topics of review. The main function of TP53 in the normal organism is consistent with its role as a 'guardian of the genome' which eliminates potentially dangerous cells in embryonic development and in proliferating adult tissues. Effects of TP53 are tissue specific and are determined by tissue specific transcription of the TP53 gene and other members of the TP53 pathway.