A limitation of the approach is that proteins must first be amenable to analysis by MS. Additionally, low crosslinking yields can inhibit the detection of hits. Advances in protein mass spectrometry and development of photoreactive groups with improved crosslinking yields will improve the applicability of the approach. We anticipate the accessibility of the PhABit workflow will enable efficient identification of fragment binders to emerging biological targets. Furthermore, the informative output of the various follow-up studies will facilitate the rapid development of tool molecules for disease biology and target validation studies.