The p53 tumor suppressor exerts anti-proliferative effects, including growth arrest, apoptosis and cell senescence, in response to various types of stress. Tight regulation of p53 activation is imperative for preventing tumorigenesis and maintaining normal cell growth; p53 stabilization and transcriptional activation are crucial early events in a cell's battle against genotoxic stress. Ubiquitination, phosphorylation and acetylation are post-translational modifications to p53 that affect its overall appearance and activity. Recent findings suggest that these modifications have a profound affect on p53 stability and function. Defining the precise roles of these modifications in p53 function may show not only that they are markers of the stress response but also that they serve as the focal point in the regulation of p53.