The mechanisms responsible for the clearance and recognition of intravenously injected liposomes by phagocytic cells of the reticuloendothelial system are presently not well understood. Here, we address a multiplicity of physicochemical and physiopathological factors which influence the clearance kinetics and tissue distribution of liposomes administered into the circulation. Emphasis is particularly drawn towards the concept of liposome-blood protein interaction and its role in liposome recognition by various phagocytes of the reticuloendothelial system.