Cyclophosphamide is a potent immunosuppressive agent that has an important role in the treatment of autoimmune, neoplastic, granulomatous, and neutrophilic disorders. Pulse intravenous cyclophosphamide has been shown to be efficacious for several dermatologic disorders, particularly pemphigus vulgaris, with a low incidence of toxicity reported. As reported earlier, studies performed on the use of pulse intravenous cyclophosphamide in the treatment of a variety of dermatology-related diseases strongly suggest that the toxicities frequently noted with the use of oral cyclophosphamide therapy may be significantly less common with pulse intravenous administration of cyclophosphamide. The short follow-up period of patients treated with this modality so far, however, requires constant vigilance for the development of side effects, particularly secondary malignancy. At this time, pulse intravenous cyclophosphamide is a promising treatment modality with an acceptable risk profile for moderate-to-severe dermatologic diseases recalcitrant to standard therapy. Prospective comparative trials are needed to assess further the efficacy and toxicity of this therapy.