The p53 protein, the product of a tumour suppressor gene, is a key regulator of cell growth, differentiation and apoptosis. It is able to induce a transient cell cycle arrest and terminal senescence. Most of its functions are exerted by the transcriptional activation of genes involved in cell cycle control, DNA repair and apoptosis. The activation of p53 is primarily mediated by post-translational modifications that affect its conformation and capacity to bind to several proteins, resulting in its stabilization and enhanced DNA-binding potential. Another way to regulate the biological function of p53 involves changes in its intracellular distribution. This paper presents an overview of the role of p53 in cellular senescence and the regulation of p53 activity by its intracellular distribution.