While the pathogenesis of inclusion body myositis (IBM) remains undetermined, there are two major hypotheses: the autoimmune hypothesis and the degeneration hypothesis. Herein, we review these hypotheses as well as potential therapeutic approaches. Evidence in favor of a primary autoimmune etiology includes the frequent complication of other autoimmune diseases in patients with IBM and the presence of autoantibodies against cytosolic 5'-nucleotidase 1A. Interleukin (IL)-1β reportedly leads to accumulation of amyloid β via nitric oxide stress in vitro. The degeneration hypothesis addresses the following aspects of IBM: accumulation of amyloid β and other abnormal proteins that are observed in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease; relation to aging; and poor response to immunotherapy. Overexpression of IL-1β in skeletal muscles of patients with IBM and its secretion from skeletal muscle cells suggests an important role for IL-1β in the pathogenesis of IBM. Thus, IL-1β is a potential treatment target.