Bovine milk proteins account for 10% of the global protein supply, which justifies the importance of thoroughly understanding their digestive processes. Extensive research on digestion is being conducted both in vivo and in vitro. However, interpretations and comparisons across different studies require a thorough understanding of the methodologies used. Both the rate and extent of milk protein digestion can be affected by several intrinsic and extrinsic factors with potential implications for overall digestibility and physiological responses. Among intrinsic factors, the impact of genetic variants in native milk proteins has emerged as a growing research area. To these, further complexity is added by the processing conditions frequently applied to milk prior to consumption. The main aim of this work is to provide an overview of the current knowledge on the impact of variations in milk protein profiles (particularly whey: casein ratio and protein polymorphisms), the treatments applied during processing (pasteurisation, homogenisation) and consumption (temperature changes) on protein digestion. To support the interpretation of the current literature, this manuscript also presents a historical perspective into research in this field and summarizes the protocols that are most frequently used, presently, on in vitro digestion studies.