Covering: up to the end of 2024Breastfeeding is one of the most effective ways to promote child health. However, characterizing the chemistry that fortifies the benefits of breastfeeding remains a grand challenge. Current efforts in the community are focused on characterizing the roles of the different carbohydrates, proteins, and fats in milk. The goal of this review is to highlight and describe current knowledge about the major classes of macromolecules in human milk and their potential role in infant health and wellness.