Plasma cell dyscrasias are a group of clinically and biochemically diverse disorders of unknown etiology, characterized by the disproportionate proliferation of one or more clones of B cells, and the presence of a structurally and electrophoretically homogeneous (monoclonal) immunoglobulin or polypeptide subunit in serum or urine. The role of splenectomy in the management of plasma cell dyscrasias has not been well defined. Using MEDLINE, the authors searched the English-language published literature from the year 1970 through September 2005 to determine the indications for splenectomy in plasma cell dyscrasias. A review of the literature in humans and animals supported the idea that the spleen provides a special microenvironment favorable for homing or differentiation of IgM producing B cells, and splenectomy can, at times, lead to remission in Waldenström's macroglobulinemia. The other reported reasons for splenectomy in plasma cell dyscrasias are hypersplenism-related pancytopenia, control of splenic plasmacytomas, and management of a splenic abscess. Splenic infiltration in primary amyloidosis can be an indication for splenectomy, where removal of a large spleen can also reverse an acquired factor X deficiency. Thus, the spleen can be considered a potential target organ for management of plasma cell dyscrasias, and therapeutic success has been achieved with removal of this organ. However, splenectomy can be a potentially morbid procedure in patients with plasma cell dyscrasias, and major postoperative complications include infection, hemorrhage, and thrombosis.