Fragment based drug discovery is gaining acceptance as a complement to other more established techniques to identify leads and optimize drug candidates. In this review we illustrate areas where fragment based drug discovery has had an impact and point to some examples that show how fragment based analysis is being applied to new arenas. The traditional uses of computational methods in fragment based for lead discovery and optimization and for risk assessment are briefly summarized. The application of fragment analysis for the definition of bioisosteric replacements are discussed together with techniques to characterize the diversity of chemical libraries based on fragment distribution.