Orofacial granulomatosis (OFG) encompasses conditions characterized by non-necrotizing granulomatous inflammation of the oral and maxillofacial region that present clinically as labial enlargement, perioral and/or mucosal swelling, oral ulcerations, and gingivitis. The unifying term “OFG” has been introduced to integrate the spectrum of various disorders, including Melkersson-Rosenthal syndrome and granulomatous cheilitis (which is sometimes considered to be a monosymptomatic form of Melkersson-Rosenthal syndrome), and has been shown to be associated with Crohn's disease, sarcoidosis, and infectious diseases such as tuberculosis. Although various etiological agents such as food substances, food additives, dental materials, and various microbiological agents have been implicated in the disease process, its precise pathogenesis is yet to be elucidated. Delayed type of hypersensitivity reaction appears to play a significant role, although the exact antigen inducing the immunological reaction varies in individual patients. However, evidence for the role of genetic predisposition to the disease is sparse. The underlying immunological mechanism appears to show some similarities between OFG and Crohn's disease, emphasizing the need for more comparative studies of the two entities. The aim of this article is to report a case of OFG, along with a detailed literature review of the facts and variations associated with its nomenclature, clinical presentation, and etiology. It also projects the challenges that a professional has to face in the diagnosis and treatment planning of such cases.