Pemphigus is a life-threatening autoimmune bullous disorder that requires long-term treatment with systemic corticosteroids mostly in conjunction with further immunosuppressants. Rituximab has opened a new avenue for severe and refractory pemphigus patients. In 95% of the 136 pemphigus patients reported to date in the English, French, and German literature, at least a partial remission has been achieved. In about two-thirds of communicated cases, application of rituximab resulted in the healing of all lesions. A controlled prospective study, however, has only recently being initiated. In pemphigus, rituximab is aimed at resetting the immune system to a condition in which autoreactive B lymphocytes are eliminated or sufficiently controlled. Here, we review mechanisms of action, different treatment protocols, clinical responses, and the safety profile of rituximab.