As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development.  Fragments in a small library, with lower molecular mass and high “ligand efficiency”, are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods.  Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good “drug-like” lead and candidate compounds.  In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.