Because of the relatively nonspecific clinical findings associated with a variety of granulomatous diseases, a microscopic diagnosis of granulomatous inflammation often presents a diagnostic dilemma for the clinician. The most common differential diagnosis includes foreign body reactions, infection, Crohn's disease, sarcoidosis, and orofacial granulomatosis. However, a variety of other conditions may be associated with granuloma formation. Often an extensive clinical, microscopic, and laboratory evaluation may be required to identify the source of the granulomatous inflammation. This article highlights the origin, clinical manifestations, current diagnostic modalities, and treatment of specific granulomatous diseases that may be encountered in clinical practice.