Over recent decades a number of genes causing predisposition to cancer have been identified. Some of these cause rare autosomal dominant monogenic cancer predisposition syndromes. In the majority of families, the increased incidence of cancers is due to a multifactorial aetiology with a number of lower penetrance cancer predisposition genes interacting with environmental factors. Identification of those at increased risk of cancer on account of their family history is important, as genetic testing, enhanced surveillance, prophylactic surgery and chemoprophylaxis may be indicated. In this article the issues surrounding genetic predisposition to cancer are considered by examining two common cancers: colorectal and breast cancer.