The office practice of dermatology is challenged when encountered by rare but potentially fatal autoimmune blistering diseases. Many of these diseases at various time points during their clinical course may involve one or more mucosae. These diseases have been at the cutting edge of laboratory research, and consequently much information has been obtained about their pathogenesis. These diseases provide another challenge because their treatment warrants the use of relatively high doses of systemic corticosteroids and immunosuppressive agents. This aspect has assumed greater importance because in recent years it has often been demonstrated that death in such patients is frequently a consequence of incorrect or inappropriate therapy. From the perspective of office dermatology, these diseases have three unique and critical dimensions. First, they are exceedingly rare, and unless there is a high index of suspicion, the diagnosis can be missed easily. Second, the availability of diagnostic tests and facilities are within a short reach of almost all dermatologists in the United States so that not having access to such facilities cannot justify any delay in their diagnosis. This is particularly important because early diagnosis, almost invariably, results in rapid improvement and better prognosis. Third, these diseases, similar to some other specialized areas of dermatology, are often better handled by individuals who have sufficient experience in their diagnosis and management. The treating clinician invariably will be doing the patient a service by referring the patient to the closest expert in immunodermatology or someone who has demonstrated a keen and concentrated interest in vesiculobullous diseases.