A crucial unresolved issue about the genotoxic stress response is how the activation of the p53 tumor suppressor can lead either to cell cycle arrest and DNA repair or to apoptosis. p53 is one of the most important tumor suppressor proteins in the cell to prevent to heritable transfer of damaged DNA. In response to different stress conditions p53 rapidly accumulates and functions as a sequence specific DNA-binding transcription factor to regulate a large number of target genes. Activation of p53 has two major outcomes: cell cycle arrest or apoptosis. In this review we attempt to enumerate the different modifications and co-factors that influence p53 promoter selection and demonstrate how p53 chooses life or death for the cell.