Food digestion is a complex biological process requiring various interrelated physicochemical actions. Food is broken down in the digestive tube by enzymatic reactions, mechanical forces, and nutrients are transported by advection, diffusion… Limiting steps in such a complex system are difficult to identify and to quantify experimentally, making it necessary to develop models and simulations. In this chapter, historical macroscale modeling based on transport phenomena (mainly mass or momentum transfer) is presented. Then, microscale modeling where the food structural features are considered is introduced. Finally, recent microscale simulations based on multi-agent systems are described. Applications to drug, protein, carbohydrate, and lipid absorption are addressed, with an emphasis on lipid digestion.