Finding novel compounds as starting points for optimisation is one of the major challenges in drug discovery research. Fragment-based methods have emerged in the past 10 years as an effective way to sample chemical diversity with a limited number of low molecular weight compounds. This information can be used to inform the design of new compounds with increased affinity, specificity and novelty, especially if the ternary complex structures of the fragments binding to the protein can be solved. In FBDD about 1000-1500 low molecular weight fragments are typically screened using biophysical techniques. Ideally, the experimental binding mode will be established by X-ray crystallography. Fragments are then grown to form new interactions as shown schematically below. Although fragment hits have low potency due to their small size, they form high quality interactions and can readily be optimised into potent lead molecules and ultimately clinical candidates.