Abstract Purpose of Review: Inclusion body myositis (IBM) is an enigmatic progressive disease of skeletal muscle. This review provides a summary of the clinical and pathophysiologic aspects of IBM. Recent Findings: The development of diagnostic blood testing for IBM followed from the discovery of a B-cell pathway in IBM muscle and circulating autoantibodies against NT5C1A, further establishing IBM’s status as an autoimmune disease. The key role of cytotoxic T cells in IBM is further supported by the identification of a link between IBM and T-cell large granular lymphocytic leukemia. The testing of research diagnostic criteria in patients is improving its accuracy. Increases in estimated prevalences may be due to a combination of true increases and improved recognition of disease. Summary: IBM has high unmet medical need. Advances in the mechanistic understanding of IBM as an autoimmune disease will drive effective therapeutic approaches. The identification of a B-cell pathway has resulted in the first identification of an IBM autoantigen and emphasized its status as an autoimmune disease. The recognition that large granular lymphocyte CD8+ T-cell expansions are present in both blood and muscle provides additional biomarkers for IBM and suggests a mechanistic relationship to the neoplastic disease T-cell large granular lymphocytic leukemia. Author Information Address correspondence to Dr Steven A. Greenberg, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115, [email protected]. Relationship Disclosure: Dr Greenberg has served as a consultant for Acceleron Pharma and Novartis AG and receives research/grantsupport from the Inclusion Body Myositis Foundation, Inc and Pfizer Inc. Dr Greenberg receives licensing fees from MedImmune and publishing royalties from UpToDate, Inc. Unlabeled Use of Products/Investigational Use Disclosure: Dr Greenberg reports no disclosure. Copyright © 2016 by the American Academy of Neurology.