Subepidermal autoimmune bullous disorders are a heterogeneous group of diseases that are associated with autoantibodies to hemidesmosomal proteins (pemphigoid group, epidermolysis bullosa acquisita) or epidermal/tissue transglutaminase (dermatitis herpetiformis). Characterization of the target antigens has led to the description of novel entities such as anti-p200 pemphigoid and has greatly facilitated the diagnosis of these diseases. Precise identification of target antigens is of therapeutic relevance since treatment options may greatly differ between these disorders. By the use of various in vitro and in vivo systems, the pathogenic relevance of autoantibodies to different hemidesmosomal constituents, including BP180 (type XVII collagen), laminin 332 (laminin 5), α6β4 integrin, and type VII collagen has been demonstrated. The translation of this basic scientific work has subsequently led to the development of specific autoantibody detection systems that are not only of diagnostic use but also allow the monitoring of circulating autoantibody levels during the course of the disease and thus are helpful in guiding treatment decisions in these patients.