P emphigus vulgaris (PV) is a rare, life-altering disease that is most likely to occur in individuals with one of two known human leukocyte antigen haplotypes. In Asian populations, the risk of developing the disease is linked to aDR6 allele, while in individuals of Ashkenazi Jewish ancestry, the linkage is with the DR4 haplotype DR B1*0402. The disease shows an estimated incidence of 1/100,000 individuals yearly. PV, the most common form of pemphigus, typically develops during mid-life and is prone to remissions and relapses. The clinical presentation is insidious, with the development of persistent and steadily worsening painful ulcers in the mouth. After a variable period of time, painful blisters and erosions then arise on the head and neck, and subsequently the disease extends to involve the trunk and extremities. In extreme variants, the majority of the skin surface is denuded. Before the use of systemic corticosteroids in the 1950s, the mortality rate was estimated at 50% at two years, and approached 100% at five years. The use of corticosteroids and immunosuppressive drugs has reduced the mortality rate to less than 10%, but serious morbidities from drug side effects are still common. The patients that do succumb usually die, not directly from the disease, but from complications of immunosuppressive treatment such as overwhelming infection. Throughout the past 60 years, key advances have occurred that have enhanced our ability to diagnose, treat, and understand the pathogenesis of PV. In 1941, Civatte described the histology of PV. This description served to define the key diagnostic criteria of acantholysis; namely, a vesicle or bulla resulting from detachment of differentiating ker-