Our knowledge of the basic biology of telomeres is now beginning to yield fundamental insights into the pathophysiology of complex human diseases including cancer. Telomeres cap chromosome ends and thereby prevent the ends from being recognized as free DNA double-stranded breaks, which activate p53-dependent DNA damage response systems and could produce illegitimate chromosomal fusions. Studies in model organisms, including the mouse, have demonstrated that loss of telomeric sequences results in increased chromosomal instability, activation of telomere checkpoint responses (eg, cellular growth arrest and apoptosis), multisystem degeneration, and premature aging (1–4). The tumor suppressor p53 plays a key role in sensing and mediating the telomere checkpoint response. Analyses of the telomerase-deficient mouse system have established that p53 inactivation enhances the survival of cells with short, dysfunctional telomeres but generates wholesale genomic changes that drive the neoplastic process (5–7). These observations in the mouse are complemented by analyses of staged human colon and pancreatic cancers, showing an association between the onset of telomere dysfunction and chromosomal instability during early carcinogenesis, consistent with a role for telomere dysfunction in cancer initiation (8–12). Given the pivotal impact of telomeres in degenerative and neoplastic diseases, recent studies have assessed whether telomere length was associated with the risk of developing these diseases and/or might serve as a prognostic marker for established disease. To date, telomere length determinations in the