Autoimmmune bullous diseases of skin and mucosa are uncommon, disabling, and potentially lethal diseases. For a quick and reliable diagnosis immunofluorescence is essential. This article describes two variants of immunofluorescence. The direct method uses a skin or mucosal biopsy of the patient to detect in vivo bound antibodies. Indirect immunofluorescence uses patient's serum and a substrate to visualize circulating autoantibodies. These two methods supplemented with advanced techniques allow reliable classification of autoimmune bullous diseases; not only the main entities pemphigus and pemphigoid, but also subclasses within these groups. This is important because prognosis and therapy vary among different variants of autoimmune bullous diseases.