Understanding of cell membrane organization has evolved significantly from the classic fluid mosaic model. It is now recognized that biological membranes are highly organized structures, with differences in lipid compositions between inner and outer leaflets and lateral structures within the plane of the bilayer, known as lipid rafts. These organizing principles are functionally important in terms of protein localization and signal transduction as well as intercellular signaling. However, the mechanisms and biophysical basis of lipid raft formation, structure, dynamics and function are not clearly understood. One key question, which we focus on in this talk, is how lateral organization and leaflet compositional asymmetry are coupled.