Human milk fat (HMF) is the component that supplies the highest fraction of the infants required dietary energy. Other sources of fat are necessary and crucial for infants while the breastfeeding is not possible, desirable or sufficient. There is enough scientific evidence that suggests the composition and distribution of the fatty acids affect the absorption of the fat in infants greatly, which influences the growth and health of infants. However, the composition and distribution of the fatty acids in certain fat such as cow milk fat or vegetable oil are different from those in human milk. So as to mimic human milk fat composition and structure, a series of human milk fat substitutes (HMFS) have been developed through enzymatic interesterification reaction during recent years. This review described current trends in the production of HMFS, discussed the significance and methods of preparing HMFS and the problems and put forward potential solutions about this kind of product.