A functionally heterogenous class of genes, ranging from nuclear transcription factors to cell adhesion molecules having as their common denominator that their function must be compromised during development and progression of a given tumor. The most important and most widely studied tumor suppressor is called p53. Its importance becomes evident from the fact that mutations in its gene are found in approximately 50% of all human cancers, thus constituting the most frequent alteration in a single human cancer-associated gene. The prevalence of p53 mutations in human cancer has spurred research worldwide to decipher p53 functions. It is now clear that the major function of p53 is to preserve the integrity of the genome of a cell under various conditions of cellular stress, endowing p53 with the title “guardian of the genome,” coined by David Lane, one of the discoverers of p53 in 1979.