The p53 tumor suppressor gene encodes for a transcription factor that plays a seminal role in the responseof mammalian cells to physiological and environmental stress. p53 has been implicated as a majormediator of cell cycle arrest and/or apoptosis in the response of mammalian cells to stress stimuli Itappears that several determinants, including cell type, the presence or absence of survival factors in theexternal environment, the extent of DNA damage, the level of p53 and post-transletional modifications,are involved in the choice between cell cycle arrest and apoptosis. Ongoing work on the biologicalfunctions of the p53 tumor suppressor in different cell types and under various physiological conditionswill help to unravel the complex nature of molecular circuits that orchestrate the biological response top53 activation.