Chirality has become a key theme in drug discovery and development. As highlighted by Agranat and colleagues, most new drugs are now marketed as single enantiomers, and the strategy of 'chiral switches' to extend the lifespan of racemic drugs that have patents close to expiry has become well established. The second Review, by De Meyts and Whittaker, discusses the structural biology of insulin and insulin-like growth factor 1 (IGF1) receptors and the implications for the design of drugs that target them, such as orally available small-molecule insulin mimetics for the treatment of type 2 diabetes, a disease that is expected to reach epidemic proportions. Osteoporosis and other bone diseases are also anticipated to become increasingly prevalent, and the potential for the translation of the advances in the understanding of the biology of bone turnover into new therapeutics for such disorders is reviewed by Goltzman. The Reviews section is completed by two articles focusing on receptors. The Toll-like receptor (TLR) family is receiving considerable attention as a potential regulator of the immune response, and the possible use of TLR agonists or antagonists in chronic inflammatory diseases is described by Walker and colleagues. And in their Review, George and colleagues discuss how the recent realization that many G-protein-coupled receptors form multimeric complexes could provide novel paths for drug discovery. The development of many new drugs has been facilitated greatly by the Orphan Drug Act (intended to stimulate the development of therapeutics for rare diseases) in the two decades since it was passed, as highlighted by Haffner and colleagues in the first Perspective. And in the final article, Bond provokingly suggests that following the 'best' hypothesis might sometimes block the route to new drugs.