Fragment based drug discovery (FBDD) has become an increasingly important tool for finding hit compounds for difficult targets. The technique utilises smaller than drug-like compounds to identify low potency, high quality leads. Libraries containing hundreds to thousands of compounds achieve similar coverage of chemical space as the millions required for traditional high throughput screening (HTS) campaigns. A major challenge of fragment screening is that, although fragment sized compounds make high quality interactions with their targets and bind with high ligand efficiency, overall binding affinity is typically weak due to their small size. Of the many suitable biophysical techniques, X-ray crystallography was one of the first to be used, and is the most directly informative. In addition, X-ray crystallography has recently seen an order-of-magnitude speed-up thanks to robotics, improved algorithms and detectors and technical advances at synchrotron facilities. As a consequence, X-ray crystallography is now a viable primary screen for academic and industrial researchers.