This article is the fourth of five in a series on the effects of age-related changes in impairment evaluations as defined by the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth and Sixth Editions. The present article addresses the musculoskeletal system and differs from the first three articles, which focused on apportionment of an impairment rating between aging and other causes. The medical literature supports the notion that age-related osteoarthritis (OA) changes in the hand and digits frequently are associated with injury and/or repetitive motion. Thus, apportionment is indicated, but deciding which came first, the imaging abnormality or the injury, requires consummate skill on behalf of the rating physician. OA also occurs in the knees and hips of older individuals. Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory disorder characterized by calcification and ossification of spinal ligaments and entheses and is unique, in the authors’ opinion, because of a positive correlation between aging and back pain caused by this condition. The article also addresses the association—or the lack thereof—between pathology and aging, as well as degenerative changes and symptoms, to facilitate causation analysis. For a fuller discussion of causation analysis for the spine, readers can consult the AMA Guides to the Evaluation of Disease and Injury Causation, Second Edition.