Inflammatory reactions of the spleen occur in the context of two pathophysiological settings. First, lymphoid hyperplasia of the spleen can be the result of a principally physiological production of immune effector cells e.g. due to systemic viral infections, autoimmune diseases and acquired or inherited immunodeficiencies. Second, the spleen itself may be the target of a pathological inflammatory reaction; this setting is exemplified by abscess formation due to septicopyemic spread of bacteria and by granulomatous inflammations, e.g. due to tuberculosis or sarcoidosis. Differential diagnostic considerations have to include splenic inflammatory pseudotumors, mycobacterial spindle cell tumors and lymphomas with granulomatous or histiocyte-rich reactive changes.