Granulomas are aggregates of macrophages, often admixed with other inflammatory cells, which usually result from chronic antigen presentation. Many diseases that produce granulomas involve the liver. Some are intrinsic hepatic diseases, whereas others are disseminated systemic diseases that involve the liver and other organs. Hepatic granulomas are reportedly present in 2% to 10% of all liver biopsy specimens examined in general practice, and of those supposedly as many as 36% have no discoverable etiology even after extensive evaluation of the specimen. This review focuses on the diagnosis of granulomas in infectious diseases affecting the liver, including use of special stains, serologic studies, and molecular diagnostic techniques, and discusses pertinent noninfectious causes of hepatic granulomas that are in the differential diagnosis.