A review. Human breast milk provides the optimum nutrition for infants. Designed to provide balanced nutrition, human breast milk naturally meets the needs of growing infants in the first months after birth. In human breast milk, and in most infant formulas, approx. 50% of the energy is supplied to newborns as fat, of which more than 98% is in the form of triglycerides. Triglyceride synthesis occurs in the mammary gland. The fatty acids are specifically positioned to sn1, sn2 or sn3 positions on the glycerol backbone to yield the structure-specific triglycerides that are found in human milk. Palmitic acid (C16:0) is the predominant saturated fatty acid, comprising 17-25% of the fatty acids in mature human milk. Surprisingly, the positioning of palmitic acid is highly conserved across populations, and approx. 70-75% of palmitic fatty acids are esterified to the sn2 position of the triglyceride (sn2 palmitate). Clin. and pre-clin. studies over the last three decades have provided increasing evidence that this specific positioning of palmitic acid on the triglycerides in human milk has a significant holistic effect on optimal infant development and well-being that is related to the increased absorption of both palmitic acid and calcium: softer stools, increased bone strength, increased beneficial gut flora, controlled intestinal health, and reduced infant crying. All of these contribute to the benefits of infant wellbeing. The overall aim of the current review is to expand the understanding of the role of palmitic acid and its specific sn2 position in infant nutrition.