Pemphigus vulgaris, foliaceous, and vegetans are potentially fatal, autoimmune, vesiculobullous mucocutaneous diseases. In order to prevent potentially fatal infection and other complications, most patients with pemphigus require treatment with systemic corticosteroids and immunosuppressive agents, although these medications often cause chronic and serious adverse effects. Many case reports and several trials have documented remissions and clinical improvement in cases of pemphigus recalcitrant to standard therapy, who were treated with either intravenous immunoglobulin (IVIG) or rituximab, alone or in combination with each other. Collectively, the body of evidence from these reports is large enough to spark consideration of these treatments early in the management of pemphigus. Among the potential benefits of a therapeutic strategy that includes these biologic agents are more rapid induction of remission, prevention of corticosteroid-related adverse effects, and decreased cost of therapy. Considering the outcomes from recent trials with these novel therapies, reevaluation of the best-practice treatment of pemphigus seems prudent and timely.