The perception of flavor is a complex phenomenon, resulting from the activation of sensory receptors sensitive to stimuli of different nature, including chemical and physical stimuli. The detection of chemicals relies on the activation of chemoreceptors. Aroma compounds bind to olfactory chemoreceptors, sapid molecules to a taste chemoreceptor, and trigeminal molecules to transient receptor potential channels. These same channels can be activated by temperature. However, food is never in direct contact with the chemoreceptors; as a result, flavor compounds have to be released from food before being transported by saliva or air. During this last step, different perireceptor mechanisms can also take place, especially in the mouth during food consumption. These include, for example, partitioning between different phases (food matrix, saliva, air of the buccal cavity), non-covalent interactions but also enzymatic biotransformation. Many studies have reported the influence of the intrinsic physicochemical properties of flavor molecules such as hydrophobicity or volatility to describe the partitioning mechanisms. However, linear model based on these properties failed to explain the behavior of compounds of different nature in presence of saliva. Recent findings suggest that salivary proteins and their properties such as enzymatic conversion could play a role, beside physicochemical mechanisms. The oral enzymatic biotransformation of flavor molecules in the mouth impacts both the quality and the quantity of flavor molecules. Indeed, the concentration of the metabolized molecules decreases while the resulting metabolites can activate other chemoreceptors. According to some pioneer studies, this oral metabolism has an impact on the perception of flavors. Interestingly, the entailed enzymatic activities are subject to inter-individual variations and could be an important factor to be taken into account when investigating the origin of food preferences. In this chapter, we review the current state-of-the-art on the mechanisms of biotransformation of flavor molecules in the mouth and their importance for the sensory perception of food. Although few studies have been carried out on this emerging topic, in-mouth flavor metabolism should be taken into account in the future when designing food products, as it might explain interindividual variability of perception.