Dermatomyositis (DM) is an autoimmune disease mainly affecting muscle and skin. Typical clinical and laboratory findings include muscle weakness with elevated muscle enzymes, characteristic skin lesions (e.g., Gottron papules, heliotrope erythema, Shawl sign), and specific serum autoantibodies. Recent studies have highlighted the activation of the innate immune system, including high expression of interferons (IFNs) and IFN-regulated proteins, as an important pathological hallmark of DM. These findings have changed our understanding of the disease fundamentally, since inappropriate activation of the innate immune system with secondary dysregulation of the adaptive immune response is now considered to be a central pathogenetic feature of DM. In this article, we review current guidelines and standards in diagnosis and treatment. We detail evidence-based and pathophysiology-based treatment strategies, with a focus on skin as well as on muscle lesions. Particularly, we discuss how the recent advances in the understanding of the pathomechanisms of DM have altered our conception of the mode of action of established drugs such as chloroquine and methotrexate. Finally, we outline possible future treatment strategies, with a focus on the innate immune system, e.g., targeting the IFN system with the anti-IFN-α antibody sifalimumab.