The milk fat globule membrane (MFGM) is avidly studied by many groups of scientists around the world and is yielding very important new information. Its structure, complex and heterogeneous, doesn't fit into the norms of physical and chemical studies. The structure of the MFGM is not static, it changes constantly with its surroundings and, in particular, it changes with each different step in processing. From the simple process of cooling milk to the drastic homogenization and UHT treatments, the fate of the MFGM and its components is poorly understood in terms of its influence on digestion and nutrient delivery. The MFGM was initially described in the 1970s and 1980s as the membrane that surrounds fat globules in milk, preventing coalescence and rancidity of lipids. However, in the last 2 decades, its biologically active properties have been explored in greater detail and in different models. In fact, research has ascribed to MFGM anticancer and antihypercholesterolemic activities, antimicrobial and antiviral properties such as inhibition of the ulcer-forming bacterium Helicobacter pylori and rotavirus, and suppression of diseases such as multiple sclerosis. In addition, in clinical studies, complementation of infant food with MFGM and micronutrients has led to new products with great potential for the health and wellness of consumer, especially babies. We propose that the composition and structure of the MFGM in milk plays a central role in the digestion of fat both the rate and extent of digestion. The structural studies presented here are based on the phospholipid characterization, on protein analysis, bacterial binding and microscopy observations on native and processed MFGM. Bacterial interactions have been studied by a combination of gradient centrifugation procedures, fluorescent tagging and binding, and confocal microscopy. In addition, some of the changes to the MFGM proteins during milk processing have been followed by proteomic techniques, particle size distribution and surface charge. We present also an important part of the milk lipids, the ectosomes and exosomes, that recently have been linked with functions in nutrition and health. Results of these studies have proven useful in finding relevant information from this complex system.