The bioavailability of dietary lipophilic components may be either increased or decreased by manipulating the microstructure and/or physicochemical properties of the foods that contain them. This article stresses how knowledge of the molecular, physicochemical, and physiological processes that occur during lipid ingestion, digestion, and absorption can be used to rationally design food structures to control these processes and therefore impact the rate or extent of lipid digestion and/or absorption. These approaches include controlling the molecular characteristics of the lipid molecules, altering lipid droplet size or interfacial properties, and manipulating food matrix structure and composition. Improved knowledge of the molecular, physicochemical, and physiological processes that occur during lipid ingestion, digestion, and absorption will facilitate the rational design and fabrication of functional foods for improved health and wellness.