Fatty acids undergo different metabolic fates depending on their chain length and degree of saturation. The purpose of this review is to examine the metabolic handling of medium chain fatty acids (MCFA) with specific reference to intermediary metabolism and postprandial and total energy expenditure. The metabolic discrimination between varying fatty acids begins in the GI tract, with MCFA being absorbed more efficiently than long chain fatty acids (LFCA). Subsequently, MCFA are transported in the portal blood directly to the liver, unlike LCFA which are incorporated into chylomicrons and transported through lymph. These structure based differences continue through the processes of fat utilization; MCFA enter the mitochondria independently of the carnitine transport system and undergo preferential oxidation. Variations in ketogenic and lipogenic capacity also exist. Such metabolic discrimination is supported by data in animals and humans showing increases in postprandial energy expenditure after short term feeding with MCFA. In long term MCFA feeding in animals, weight accretion has been attenuated. These differences in metabolic handling of MCFA versus LCFA are considered with the conclusion that MCFA hold potential as weight loss agents.