The spleen performs essential functions in the turnover of erythrocytes. It removes erythrocytes, metabolizes hemoglobin, and recycles iron. The spleen also mounts a primary immune response to antigens in the blood and synthesizes antibodies in its white pulp. Human splenic endothelial cells (HSEC), similar to other endothelial cells, constitute the natural interface between the blood and the underlying tissue. Previous studies have demonstrated an intriguing link between splenic endothelial cells, splenic hamartoma and capillary hemangioma. Splenic endothelial cells have also shown a supportive micro-environment for the development of dendritic cells. Furthermore, rapid destruction of young erythrocytes can occur in the spleen due to altered endothelial cell-macrophage interactions. These observations suggest that splenic endothelial cells may play a more compelling role in the mononuclear phagocyte system.