In this short review, we examine the overlap between genes known to be mutated in the germlines of individuals at risk of breast, ovarian and prostate cancers, and their positions in DNA damage repair pathways. Cancer risk mutations have been consistently reported in certain genes at the top of these pathways, but none have been reported in others. We consider whether some of these gene products are too crucial to life for mutations to be tolerated, whilst others, further down the pathways, are less essential.