Summary The genetic component of human longevity is estimated at 30%. Which genes are involved in determining human longevity, however, is largely unknown. Genes that may affect human survival are susceptibility loci for major age-related pathologies. Many studies are being performed to identify such loci for cardiovascular disease, dementia and diabetes. In order to establish how these loci relate to survival, we have initiated a genetic association study in populations of the oldest old. On the basis of the study design optimised approaches to identify loci affecting human longevity are discussed.