In the last few years, knowledge on the composition and properties of the milk fat globule membrane (MFGM) increased significantly. It is now recognized that the MFGM is highly complex in structure and composed of different protein and lipid components with specific technological and nutritional properties. As such, MFGM materials have been isolated and characterized as valuable ingredients for incorporation into new food products. However, MFGM are also sensitive to modification during isolation and processing, and care should be taken to standardize the composition and characteristics of the membrane to maintain its unique properties during application in food products. The MFGM is subject to changes in composition and structure from the moment the fat globule leaves the mammary secretory cell. Upon milk harvesting and further milk handling, further changes to the MFGM take place. Depending on the type and degree of treatment, this may involve different physico-chemical interactions between various membrane components, the loss of membrane components and/or adsorption of components from the milk plasma. However, the effects appear to be variable and dependent on physiological (animal) factors, and much remains to be learned about the phenomena on a molecular level.