The spleen is the largest secondary immune organ in the body and is responsible for initiating immune reactions to blood-borne antigens and for filtering the blood of foreign material and old or damaged red blood cells. These functions are carried out by the 2 main compartments of the spleen, the white pulp (including the marginal zone) and the red pulp, which are vastly different in their architecture, vascular organization, and cellular composition. The morphology of these compartments is described and, to a lesser extent, their functions are discussed. The variation between species and effects of aging and genetics on splenic morphology are also discussed.