Breast cancer results from genetic and environmental factors leading to the accumulation of mutations in essential genes. Genetic predisposition may have a strong, almost singular effect, as with BRCA1 and BRCA2, or may represent the cumulative effects of multiple low-penetrance susceptibility alleles. Here we review high-and low-penetrance breast-cancer-susceptibility alleles and discuss ongoing efforts to identify additional susceptibility genes. Ultimately these discoveries will lead to individualized breast cancer risk assessment and a reduction in breast cancer incidence.