Symmetric proximal muscle weakness has many potential etiologies. An onset over weeks to months and elevated serum levels of muscle enzymes point to the diagnosis of an idiopathic inflammatory myopathy, including dermatomyositis, polymyositis, and inclusion body myositis. However, there is a broad differential diagnosis, including certain muscular dystrophies, metabolic myopathies, drug- or toxin-induced myotoxicity, neuropathies, and infectious myositides. The differentiation is critical for defining appropriate treatment. In addition, an alternative diagnosis may explain the lack of response to immunosuppressive treatment for some patients with polymyositis. Careful clinical evaluation and choice of available diagnostic tests are required to establish the correct diagnosis.