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The p53 pathway has been shown to mediate cellular stress responses; p53 can initiate DNA repair, cell-cycle arrest, senescence and, importantly, apoptosis. These responses have been implicated in an individual's ability to suppress tumour formation and to respond to many types of cancer therapy. Here we focus on how best to use knowledge of this pathway to tailor current therapies and develop novel ones. Studies of the genetics of p53 pathway components — in particular p53 itself and its negative regulator MDM2 — in cancer cells has proven useful in the development of targeted therapies. Furthermore, inherited single nucleotide polymorphisms in p53 pathway genes could serve a similar purpose.