Inheritance of one defective copy of either of the two breast-cancer-susceptibility genes, BRCA1 and BRCA2, predisposes individuals to breast, ovarian and other cancers. Both genes encode very large protein products; these bear little resemblance to one another or to other known proteins, and their precise biological functions remain uncertain. Recent studies reveal that the BRCA proteins are required for maintenance of chromosomal stability in mammalian cells and function in the biological response to DNA damage. The new work suggests that, although the phenotypic consequences of their disruption are similar, BRCA1 and BRCA2 play distinct roles in the mechanisms that lead to the repair of DNA double-strand breaks.