In older adults, acute and chronic illness, including late-onset psychiatric disorders, occurs within the context of age-related alterations in physiology at the organ system, cellular, and genomic levels. Some of these changes reflect the ineluctable response to normal aging, but their onset and severity often are influenced by patient behaviors (e.g., smoking, lifestyle) and the environment (e.g., culturally influenced diets, environmental toxins). These age-related changes affect virtually all organ systems and increase the vulnerability of older adults to functional decline, disability, and organ-system dysfunction, thereby contributing to the burden of multiple comorbidities. This chapter discusses general principles of aging and age-related changes in the function of individual organ systems that should be considered by the psychiatrist in the diagnosis and management of the older psychiatric patient.