The term desquamative gingivitis (DG) refers to a clinical manifestation that can be caused by several disorders. Many of them are immunologically mediated; in addition to the oral cavity, they can affect extraoral mucocutaneous sites, e.g., larynx, conjunctiva, esophagus, nasal and genital mucosa, and the skin. The degree of oral, periodontal, and systemic involvement determines the overall morbidity and, sometimes, the mortality of these disorders. We comprehensively review disorders commonly associated with DG and highlight diagnostic pathways, guidelines for differential diagnosis, and oral, periodontal, and systemic implications. More rare conditions are reviewed as well. Mucous membrane pemphigoid, oral lichen planus, and pemphigus vulgaris are responsible for the majority of cases of DG. In addition, other uncommon disorders should be considered. Accurate clinical, histologic, and serologic investigations are often required to differentiate among DG-associated disorders, provide adequate therapy, and improve the prognosis of patients.