Fragment-based screening (FBS) has become an established approach for hit identification. Starting points identified by FBS, are small fragments that require substantial modification to become leads. As fragments are different from classical hits a process tailored for fragment evolution is required. Scores for ligand efficiency have been proposed as guides for this process. Here we review how these have been applied to guide the selection and optimization of fragment hits. © 2010 Elsevier Ltd. All rights reserved.