Telomerase is a ribonucleoprotein enzyme complex that maintains telomere length in cancer cells by adding repeats onto the telomeric ends, thus compensating for the normal erosion of telomeres that occurs in all dividing cells. The telomere-telomerase hypothesis of aging and cancer is based on the findings that immortal cancer cells have engaged a mechanism to maintain stable telomere lengths, almost always by reactivating or up-regulating telomerase activity. Ataxia telangiectasia (AT) is an autosomal recessive chromosome instability syndrome in which patients are predisposed to development of leukemia, lymphoma and sarcoma, with other tumors that are seen less frequently. Nijmegan breakage syndrome is a disorder characterized by many of the clinical features associated with AT, including immunological deficiencies, microcephaly, and developmental delay. Werner syndrome is a rare autosomal disorder characterized by features of premature aging. Fanconi anemia is yet another chromosome instability syndrome associated with cancer predisposition and telomere effects.