Molecular Diversity in Drug Design High throughput screening and combinatorial chemistry are two of the most potent weapons ever to have been used in the discovery of new drugs. At a stroke it seems to be possible to synthesise more molecules in a month than have previously been made in the whole of the distinguished history of organic chemistry Furthermore all the molecules can be screened in the same short period. However like any weapons of immense power these techniques must be used with care to achieve maximum impact. The costs of implementing and running high throughput screening and combinatorial chemistry are high as large dedicated facilities must be built and staffed. In addition the sheer number of chemical leads generated may overwhelm the lead optimisation teams in a hail of friendly fire. Mother nature has not entirely surrendered as the number of building blocks that could be used to build libraries would require more atoms than there are in the universe. In addition the progress made by the Human Genome Project has uncovered many proteins with different functions but related binding sites creating issues of selectivity. Advances in the new field of pharmacogenomics will produce more of these challenges. There is a real need to make hi throughput screening and combinatorial chemistry into smart weapons so that their power is not dissipated. That is the challenge for modellers computational chemists cheminformaticians and IT experts. In this book we have broken down this grand challenge into key tasks. Issues in Molecular Diversity and the Role of Ligand Binding Sites Molecular Diversity in Drug Design. Application to High speed Synthesis and High Throughput Screening Background Theory of Molecular Diversity Absolute vs Relative Similarity and Diversity Diversity in Very Large Libraries Subset Selection Methods For Chemical Databases Molecular Diversity in Site focused Libraries Managing Combinatorial Chemistry Information Design of Small Libraries for Lead Exploration The Design of Small and Medium sized Focused Combinatorial Libraries.