Fats and oils account for 38% of the total calories in the diet of Western populations, especially in the U.S. They provide the most concentrated source of energy, 9 kcal/g of a triacylglycerol molecule compared with 4 kcal/g provided by carbohydrate and protein. In response to consumer demands for low-calorie or calorie-free fats and their reluctance to give up the taste of fat, current research efforts have been directed toward the development of lipid-like fat substitutes. These fat substitutes contain the fatty acids found in conventional fats and oils, with all the physical and organoleptic properties of fats, but provide few or no calories in the diet. Some of the fat substitutes are modified triacylglycerols (glycerol backbone) with reduced digestion and absorption; others are digestible and nondigestible carbohydrate fatty acid esters and polyesters, respectively. Sucrose polyester (Olestra), a sucrose molecule esterified with six to either fatty acids, is the most studied of the lipid-based fat substitutes containing a carbohydrate backbone. If approved by the FDA, sucrose polyester will find application in almost all fat-containing foods. Specialty fats or fat substitutes targeted to certain individuals with special needs are being developed. Among these are the medium-chain triacylglycerols and structured lipids (glycerol backbone), or ¿nutraceuticals¿ with reduced absorption and medical applications. Enzyme biotechnology is another tool available to lipid chemists to selectively modify, esterify, transform, transesterify, and interesterify fats and oils or synthesize new lipids such as structured lipids of food, nutritional, and medical importance. These designer fats may be the trend in the future to produce medical lipids that do not occur normally in nature. The different types of lipid-based fat substitutes are reviewed with respect to their synthesis, analysis, metabolism, potential applications/uses, and the future of fat substitutes.