Much effort in recent years has been focused on understanding the factors that contribute to breast cancer risk. Two major susceptibility alleles, BRCA1 and BRCA2, have been identified, and the prevalence and penetrance of mutations in these genes have been studied extensively. However, this work highlights the fact that only a small proportion of breast cancer is due to mutations in the genes. Evidence for additional high penetrance genes exists, but it is becoming clear that an understanding of multiple lower penetrance alleles will be necessary to fully define breast cancer risk. Work in this area has focused on the analysis of polymorphisms of potential functional significance in several classes of genes, including those involved in carcinogen metabolism, oestrogen metabolite biosynthesis, steroid hormone receptor activation and DNA damage response. These studies are reviewed and a strategy to use modification of breast cancer penetrance in families with known mutations in BRCA1 as a means of identifying additional low penetrance, or modifier, genes is discussed.