Proteins are important macronutrients for the human body to grow and function throughout life. Although proteins are found in most foods, their very dissimilar digestibility must be taking into consideration when addressing the nutritional composition of a diet. This review presents a comprehensive summary of the in vitro digestibility of proteins from plants, milk, muscle, and egg. It is evident from this work that protein digestibility greatly varies among foods, this variability being dependent not only upon the protein source, but also the food matrix and the molecular interactions between proteins and other food components (food formulation), as well as the conditions during food processing and storage. Different approaches have been applied to assess in vitro protein digestibility (IVPD), varying in both the enzyme assay and quantification method used. In general, animal proteins tend to show higher IVPD. Harsh technological treatments tend to reduce IVPD, except for plant proteins, in which thermal degradation of anti-nutritional compounds results in improved IVPD. However, in order to improve the current knowledge about protein digestibility there is a vital need for understanding dependency on a protein source, molecular interaction, processing and formulation and relationships between. Such knowledge can be used to develop new food products with enhanced protein bioaccessibility.