Appropriate selection of biochemical targets is one of the most important drivers of cost effectiveness in the discovery of new medicines. Despite the many advances in genetics, genomics and systems biology, ‘validation’ of a target is not achieved until therapeutic efficacy is demonstrated by a drug candidate. Volume 46 of this series reviews the medicinal chemistry aimed at six diverse targets from which important new medicines are emerging: * HIV integrase (discovery of the first-in-class inhibitor drug raltegravir)* 11-beta-Hydroxysteroid dehydrogenase (new approach to glucocorticoid regulation)* Nicotinic a7 choline receptor (agonists and positive allosteric modulators). * Bradykinin receptor (new approach to pain therapy)* Histone deacetylase (new drugs for cancer)* 5-HT2c receptor modulators (various CNS indications)