Inflammatory muscle disease is a term used to designate a heterogeneous group of autoimmune diseases of unknown etiology whose main target is the skeletal muscle. Clinical, histological, and immunopathological criteria are classically used to distinguish polymyositis, dermatomyositis, and inclusion body myositis. Major obstacles to controlled therapeutic trials in patients with inflammatory muscle diseases include the heterogeneity of these diseases, their low prevalence, and the absence of validated evaluation criteria. To date, no such trials are available and the treatment is therefore largely empirical. Glucocorticoids are usually given first. Methotrexate is then added in the event of resistance to, or dependency on, glucocorticoid therapy. Methotrexate may be used from the outset in patients with severe disease in an attempt to decrease the glucocorticoid requirements. However, no controlled trials have been conducted to determine whether first-line methotrexate therapy improves outcomes. Intravenous immunoglobulin infusion is a costly treatment option that is reserved for the following situations: refractory dermatomyositis, based on a trial showing superiority over a placebo; myositis with impaired swallowing; and patients with contraindications to immunosuppressants. In patients who fail second-line treatment, which usually consists of methotrexate plus a glucocorticoid, the diagnosis should be carefully reappraised before other treatment options are considered. These options include methotrexate plus azathioprine and recently introduced drugs such as mycophenolate mofetil and rituximab. Caution is in order when considering TNF⍺ antagonist therapy, as cases of paradoxical exacerbation of the muscle involvement have been reported.