Protein p53 is a key player in mitochondrial mediated apoptotic cell death and excess p53 activity has been implicated in many disease states such athrosclerosis, diabetes, osteoarthritis, Alzheimers disease, Parkinsons disease, Huntingtons disease, AIDS, P. falciparum and S. typhimurium infections. Thus, chemical inhibitors of p53 activation might prove effective in suppressing diseases associated with excess p53 activity. Diverse chemical compounds are being synthesized and evaluated as potent inhibitors of p53 in many cell types. In this review, we have focused on the effects of apoptosis, which is involved in p53 protein and inhibition of p53 induced apoptosis. Peculiar features of p53 protein and its roles in various diseases are summarized along with important inhibitors developed in recent years.