Removal of intravenously injected liposomes from the circulation is achieved by cells of the mononuclear phagocyte system, also known as the reticuloendothelial system. On exposure to blood, liposomes become coated with plasma proteins; some of these proteins (opsonins) are thought to determine their recognition by mononuclear phagocytes. This review provides a critical discussion of factors that control opsonization of liposomes and their phagocytosis in vivo and in vitro.