A significant proportion of the non-infectious diseases of oral mucosa are either auto-immune in nature or have lesions which are the result of immunologically-mediated events. These include pemphigus, benign mucous membrane pemphigoid, linear IgA bullous dermatosis, dermatitis herpetiformis, epidermolysis bullosa acquisita, erythema multiforme, and lichen planus. Although each of these has certain specific characteristics, all may produce bullae, erosions, and ulcers on the oral mucosa, resulting in confusingly similar clinical presentations. With careful clinical, histological, and immunofluorescence examination, it is possible to establish a definitive diagnosis in a high proportion of cases. However, one of the most exciting developments which has emerged from recent research into these diseases is their precise molecular characterization. This raises the prospect of accurate, highly specific diagnostic tests which would provide the basis for sound clinical management, with original approaches replacing the somewhat unsatisfactory symptomatic treatment which is often all that is available.