Since the early 1990s, several technological and scientific advances — such as combinatorial chemistry, high-throughput screening and the sequencing of the human genome — have been developed for discovery of new drug entity. However, the return on investment in terms of marketed products has not met expectations. Fragment-based drug design is another tool for drug discovery that has emerged in the past decade. The goal is to build drug leads in pieces, by identifying small molecular fragments and then either linking them or expanding them. Fragment-based drug design is a new approach that has been successfully applied to challenging targets, such as protein-protein interactions. Fragment-based drug design uses x-ray crystallography, NMR or other physical techniques to screen fragment libraries for specific binding to a target protein. Knowledge of exactly how the fragments bind to the protein target allows the hits to be optimized by growing the fragments or by combining and linking different fragments.