This chapter aims to examine the strengths and limitations of the current in vitro models used for studying infant digestion (0–6 months old). It presents the key parameters of the infant digestion. The chapter gives an overview of the existing in vitro models used for studying the digestion of infant food. It discusses the future trends and challenges of infant in vitro digestion modeling. The kinetics are particularly important for the metabolic fate of the nutrients, and it is thus important to consider this aspect. In vitro models can only be useful if they are physiologically relevant; however, the relevance is always difficult to examine. A harmonized protocol needs to be reached for better comparison across laboratories and for improving the relevance of the in vitro data in order to progress in our understanding of the digestive fate of food in the infant.