Using a combinatorial process to prepare sets of compounds from sets of building blocks is called Combinatorial Chemistry. The design & synthesis of compound libraries for identification of lead structures is long and costly. Synthesis of an almost unlimited number of organic compounds covering as much of chemistry space as possible is no longer the most cost effective & time saving approach to hit identification. Creating libraries, using biological target structures to inform chemical design, facilitated by quantum advances in structural genomics and computational capabilities, is a smarter, more efficient way to produce good initial leads. Considering solubility, permeability & other drug-like properties early in library design and introducing both target & lead structural constraints in lead development are further ways to ensure more compounds make it to trial. There is not enough matter in the universe to prepare all possible combinatorial variations. Combinatorial chemistry generates lead compounds that could exhibit biological activity against a particular target. Since hundreds of thousands, even millions, of compounds can be involved, combinatorial chemistry is characterized by the vast amounts of data involved and the information management challenges they pose.