The study of rare genetic diseases can lead to insights into the cause and treatment of common diseases. An example is the rare chromosomal instability disorder, Fanconi Anemia (FA). Studies of this disease have elucidated general mechanisms of bone marrow failure, cancer pathogenesis, and resistance to chemotherapy. The principal features of FA are aplastic anemia in childhood, susceptibility to cancer or leukemia, and hypersensitivity of FA cells to DNA cross-linking agents. There are thirteen FA genes, and one of these genes is identical to the well known breast cancer susceptibility gene, BRCA2. The corresponding FA proteins cooperate in the recognition and repair of damaged DNA. Inactivation of FA genes occurs not only in FA patients but also in a variety of cancers in the general population. These findings have broad implications for predicting the sensitivity and resistance of tumors to conventional anti-cancer agents, to inhibitors of poly-ADP ribose polymerase 1, an enzyme involved in DNA repair, and to other inhibitors of DNA repair.