Older adults generally have multiple medical problems as well as subclinical changes in several physiologic systems. This special article presents a framework (based on the World Health Organization International Classification of Functioning, Disability, and Health) for organizing comorbid processes and diseases to facilitate research and assist clinicians caring for older adults. The nosology begins with physiologic systems (e.g., cardiovascular, endocrine) and assesses each system in several domains (e.g., coronary blood flow, systemic blood pressure, and cardiac function in the cardiovascular system). Functioning in each domain can range from high-functioning, even protective, zones (e.g., high levels of high-density-lipoprotein cholesterol) to severe dysfunction (as in end-stage disease). The approach has four advantages. First, it explicitly recognizes that decrements in health begin before onset of symptomatic disease. Second, it accommodates the full range of possible performance for each system instead of measuring only negative aspects. Third, it avoids arbitrary diagnostic thresholds. Fourth, it sets up an exhaustive and mutually exclusive classification system that can stimulate development of summary indices of total comorbidity burden for both research and clinical settings. As the knowledge base grows, the nosology can be updated to add new domains and refine extant ones.