Milk contains a complex set of enzymes of varying classes, along with in many cases substrates, zymogens, activators and inhibitors constituting in some instances whole systems, like the plasmin system. Some of the indigenous enzymes are present due to the way in which milk is secreted, and some have identified physiological roles, although, in many cases, these are still unclear. Subsequent processing of milk into dairy products has a range of impacts on these enzymes, in terms of partitioning, activation and inactivation. For these reasons, indigenous milk enzymes have been studied for decades to understand their technological significance (impact, positive or negative, on dairy product quality), biological role and potential use as indicators of processing efficacy. This chapter provides a short introduction to the main enzymes of significance in milk, with a specific spotlight on proteases, and then focusses on recent developments in their understanding, and challenges and research questions for the future.