Purpose of reviewThe complex biochemical composition and physical structure of the milk fat globule (MFG) are presented asa basis for its paradoxical metabolic fate: MFG is a rapid conveyor of energy through its triacylglycerol(TAG) core but contains some low-digestible bioactive complex lipids and proteins, which influence lipidmetabolism and contribute to intestinal and systemic health.Recent findingsMFG structure modulates gastrointestinal lipolysis, postprandial lipemia and even the postprandial fate ofingested fatty acids. Proof-of-concept of the nutritional programming induced by early consumption of anemulsion biomimetic of MFG compared with a typical infant formula was published in an animal model(mice). The metabolic response to a high-fat diet during adulthood was improved following neonatalexposure to the biomimetic emulsion.SummaryMFG TAG are tailored with a unique regiodistribution delivering in priority short to medium-chain fattyacids in gastric phase, an important amount of quickly metabolizable oleic acid and protecting palmiticacid in sn-2 position. MFG digestion may not only trigger rapid TAG and chylomicron plasma peaks withfast clearance but also the luminal release of nonhydrolysable bioactive compounds (glycosylatedcompounds and sphingomyelin), which contribute to intestinal and systemic health by shaping themicrobiota and modulating the immune system. These bioactive compounds form self-assembled structures,protect specific micronutrients and lower cholesterol absorption. The health benefits of MFG consumption orof some of its fractions (MFGM) under specific structures are steadily being demonstrated with still muchunsolved questions especially for populations with high nutritional needs (e.g. elderly, infants).