Fat digestion and absorption in the infant is a multistep process. An initial gastric phase of lipolysis generates modest amounts of diglycerides, monoglycerides, and free fatty acids. These initial digestion products, as well as bile salts, are required for optimal activity of the intestinal phase of lipolysis. Colipase-dependent pancreatic lipase catalyzes the intraduodenal phase of triglyceride digestion in formula-fed infants; in breast-fed infants this process is also mediated by bile salt-stimulated lipase. Triglyceride fatty acid positional distribution may modulate the efficiency of nutrient absorption. Human milk contains palmitic acid (C16:0) primarily in the sn-2 position; infant formula fat blends contain palmitic acid predominantly in the sn-1 and sn-3 positions. Because pancreatic lipase selectively hydrolyzes triglycerides at the sn-1 and sn-3 positions, free fatty acids and 2-monoglycerides are produced. Free palmitic acid, but not 2-monopalmitin (which is efficiently absorbed), may be lost as a calcium-fatty acid soap in the feces. As a result, many infant formulas contain substantial levels of well-absorbed saturated fatty acids of shorter chain lengths (e.g., C12:0) in place of palmitic acid. Means of increasing the proportion of 2-palmitic acid in infant formula may make possible fat blends closer to that of human milk with acceptable absorption characteristics.