This supplement contains a series of papers supporting the justification, design, and implementation of a longitudinal cohort study of an aging HIV-positive and HIV-negative veteran population called the Veterans Aging Cohort Study (VACS). Although the papers cover a wide range of topics and several papers address methodologic issues not unique to a study of aging veterans, all are motivated by a unifying set of assumptions. Specifically: (a) HIV/AIDS is a chronic disease in an aging population; (b) conditions among HIV-positive and -negative patients in care have overlapping etiologies; (c) individuals with pre-existing organ injury are at increased risk for iatrogenic injury; (d) cohort studies are uniquely suited to the study of chronic disease complicated by aging, comorbid conditions, drug toxicities, and substance use/abuse; (e) VACS is well positioned to study HIV as a chronic disease in an aging population.