Pemphigus is a rare autoimmune blistering disease which manifests with painful erosions and blisters of the skin and mucosa. This disorder is caused by autoantibodies attacking desmosomal proteins, necessary for cell-cell contact stability and epidermal integrity. Desmoglein (Dsg) 1 and Dsg3 are the two major target antigens in pemphigus. Yet, many other target proteins, which have been described over the years, seem to be involved in the loss of epidermal integrity. Clinical examination, combined to serological advances and detection of targeted antigens, permitted to differentiate among several pemphigus subtypes, in which pemphigus vulgaris and pemphigus foliaceus are the most common. Nowadays, serological analysis in pemphigus is a fundamental step of the diagnostic algorithm. This is based on analysis of clinical symptoms, histopathological examination of lesional skin, detection of tissue bound and circulating antibodies by direct and indirect immunofluorescence, and determination of target antigens either by enzyme-linked immunosorbent essay (ELISA) or by western blot analysis. A correct and exhaustive diagnostic algorithm is fundamental to characterize pemphigus subtypes, which lastly permits to adopt a correct treatment approach. Moreover, quality and quantity of circulating antibodies in patient's sera deliver important information regarding clinical course, disease severity and treatment response; thus, relevantly affecting physician's decision. To facilitate this process, "easy-to-perform" diagnostic kits with high sensitivity and specificity are being commercialized. In this review, we focus on available methods and established assays to correctly detect circulating autoantibodies in pemphigus. Moreover, we discuss subtype specific serological peculiarities in the five most relevant subtypes (pemphigus vulgaris, pemphigus foliaceus, pemphigus vegetans, paraneoplastic pemphigus and intercellular IgA dermatosis (also called as IgA pemphigus).