Hydrogen deuterium exchange (HDX) mass spectrometry (MS) is a powerful tool for studying structural dynamics of protein-based therapeutics. The pharmaceutical industry has become very good at finding molecules that selectively bind to proteins and inhibit or activate them. Once discovered, understanding the mechanism of action and details of target engagement are essential to moving forward. As targets become more and more challenging, finding ways to reliably obtain this information in a timely fashion have become critical. An integrated approach where the dynamics information is used synergistically with other biochemical tools has proven most beneficial. Here, 2-3 case studies are shown illustrating how HDX-MS can be used in both small- and large-molecule drug discovery.