The two major proposed uses for liposomes, i.e., drug delivery and mobilization of peripheral deposits of cholesterol, each impose requirements and restrictions on liposomal structure, particularly as it affects interactions with lipoproteins. This chapter focuses on the role of lipoproteins and apolipoproteins in (1) disrupting membrane structure and causing the leakage of liposomal contents by inducing disc formation and (2) marking liposomes for whole-particle uptake by receptors involved in lipoprotein metabolism. Control of membrane stability and whole-particle half-life can be achieved by several strategies, such as membrane stiffening, shielding the membrane surface, and increasing the dose or predosing with "empty" liposomes. The rationales and applicabilities of these strategies are discussed in the contexts of liposomes as drug delivery vehicles and as antiatherogenic particles. Directions for further basic and applied research are also presented.