Despite the massive attention it has received, there is still much to learn about the p53 tumour suppressor protein. Given that it plays complex and multiple roles in cells, it is not surprising that p53 is subjected to an intricate array of regulatory processes. p53 receives signals from cells in multiple ways, leading to its stabilization and activation. The functions of the protein are altered by phosphorylation and other covalent modifications. However, a number of proteins can regulate p53 function dramatically by noncovalent means. p53 is thus subjected to numerous signaling and regulatory pathways which we have only begun to decipher.