The basic understanding of inflammatory dermatoses and autoimmune-mediated skin disorders has greatly advanced and broadened our understanding of underlying immune mechanisms that shape the complex network of chronic inflammation and autoimmunity. The new treatment options for psoriasis exemplify how new insights into (auto)immune responses, especially the role and function of various immune cells and proinflammatory cytokines, may lead to new therapeutic strategies. The concept of targeting B cells in autoimmune-mediated disorders is closely related to the discovery of autoantibodies and their cellular origin. However, the appreciation of B cells in autoimmunity has significantly changed and is not limited to their role as progenitors of autoantibody secreting plasma cells. Recent investigations of various inflammatory skin diseases, that is, autoimmune blistering disorders, collagen vascular diseases, and atopic dermatitis, actually support the concept that B cells might be as important as T cells in the etiopathogenesis of these disorders. The striking clinical improvement seen in patients with rheumatoid arthritis following B-cell depletion with the anti-CD20 mAb rituximab has tremendously catalyzed the interest in B-cell-targeted therapies in different autoimmune diseases. Future translational and clinical investigations are mandatory to precisely define the role and the contribution of impaired B-cell function in (auto)immune-mediated skin diseases.