Abstract All membrane lipids exhibit different affinities and aversions for one another. An example of this is the strong affinity of cholesterol for sphingolipids that stabilizes lipid rafts. Cholesterol-rich lipid mixtures produce a liquid ordered phase that is midway between gel and liquid crystalline. Cholesterol–lipid affinity follows the sequence: SM > PS, PG > PC > PE and is stronger with saturated than polyunsaturated acyl chains. In addition to the conventional lipid bilayer (lamellar phase), dozens of other phases, whose functions are unknown, exist. Various lipid mixtures prefer different phases. Phase diagrams pictorially describe various lipid phases and can take a wide variety of forms. For an integral protein to achieve maximal activity, the length of its trans-membrane hydrophobic surface must match the hydrophobic length of the surrounding bilayer. The Hydrophobic Match is involved in membrane protein activity and trafficking. Lipids that normally exhibit substantial differences in their acyl chain lengths (e.g. sphingolipids) can be involved in trans-membrane coupling (interdigitation) between the inner and outer membrane leaflets.