The p53 tumor suppressor gene is the most frequently mutated gene in human cancer and, as a consequence is extensively well studied. Still, many key questions remain. For example, what does p53 do that potently suppresses cancer and how does this depend on context? How do p53 mutations act independently of p53 loss to promote cancer? Can the consequences of p53 mutations be exploited therapeutically? Our research continues to address these questions by exploring p53 action and the consequences of p53 mutations in vivo. It embraces and studies the notion that p53 action depends on context, and incorporates new genetic tools and mouse models to interrogate mechanisms of p53 mediated tumor suppression in different tissue and genetic settings. Recent work has explored how p53-mediated control of cellular metabolism can contribute to tumor suppression, and explored how tumor suppressive programs linked to p53 can be restored, at least in part, in advanced cancers.