Ceramides are sphingolipids containing a sphingosine or a related base, to which a fatty acid is linked through an amide bond. When incorporated into a lipid bilayer, ceramides exhibit a number of properties not shared by almost any other membrane lipid: Ceramides ( a) are extremely hydrophobic and thus cannot exist in suspension in aqueous media; ( b) increase the molecular order (rigidity) of phospholipids in membranes; ( c) give rise to lateral phase separation and domain formation in phospholipid bilayers; ( d) possess a marked intrinsic negative curvature that facilitates formation of inverted hexagonal phases; ( e) make bilayers and cell membranes permeable to small and large (i.e., protein-size) solutes; and ( f) promote transmembrane (flip-flop) lipid motion. Unfortunately, there is hardly any link between the physical studies reviewed here and the mass of biological and clinical studies on the effects of ceramides in health and disease.