Subepithelial vesiculobullous conditions are chronic autoimmune disorders that arise from reactions directed against components of the hemidesmosomes or basement membrane zones (BMZ) of stratified squamous epithelium to which the term immune-mediated subepithelial blistering diseases (IMSEBD) has been given. Mucous membrane pemphigoid (MMP) is the most common, but variants do exist. Non-immune disorders that involve these epithelial components typically have a genetic basis--the main example being epidermolysis bullosa. All subepithelial vesiculobullous disorders present as blisters and erosions, and diagnosis must be confirmed by biopsy examination with immunostaining, sometimes supplemented by other investigations. No single treatment reliably controls all subepithelial vesiculobullous disorders; the immunological differences within IMSEBD may account for differences in responses to treatment. Currently, as well as improving oral hygiene, immunomodulatory treatment is used to control the oral lesions of MMP, but it is not known if its specific subsets reliably respond to different agents.