Hydrogen Exchange Mass Spectrometry: Are We Out of the Quicksand?

Although the use of hydrogen exchange (HX) mass spectrometry (MS) to study proteins and protein conformation is now over 20 years old, the perception lingers that it still has "issues." Is this method, in fact, still in the quicksand with many remaining obstacles to overcome? We do not think so. This critical insight addresses the "issues" and explores several broad questions including, have the limitations of HX MS been surmounted and has HX MS achieved "indispensable" status in the pantheon of protein structural analysis tools.