In anticipation of the sequencing of the human genome and description of the human proteome, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) was initiated in 2002. AGES-Reykjavik was designed to examine risk factors, including genetic susceptibility and gene/environment interaction, in relation to disease and disability in old age. The study is multidisciplinary, providing detailed phenotypes related to the cardiovascular, neurocognitive (including sensory), and musculoskeletal systems, and to body composition and metabolic regulation. Relevant quantitative traits, subclinical indicators of disease, and medical diagnoses are identified by using biomarkers, imaging, and other physiologic indicators. The AGES-Reykjavik sample is drawn from an established population-based cohort, the Reykjavik Study. This cohort of men and women born between 1907 and 1935 has been followed in Iceland since 1967 by the Icelandic Heart Association. The AGES-Reykjavik cohort, with cardiovascular risk factor assessments earlier in life and detailed late-life phenotypes of quantitative traits, will create a comprehensive study of aging nested in a relatively genetically homogeneous older population. This approach should facilitate identification of genetic factors that contribute to healthy aging as well as the chronic conditions common in old age.