Despite the need for careful monitoring of its effects, warfarin, which was introduced more than 50 years ago, is still the main oral anticoagulant used for the prevention and treatment of thrombosis. Now, in our eighth 'Case history' article, Gustafsson and colleagues discuss the discovery of ximelagatran, the first oral anticoagulant with a novel mechanism of action to be developed in half a century. Disorders involving deficiencies in blood coagulation, such as haemophilia, are also a significant cause of morbidity and mortality, and Bishop and Lawson review recombinant biologics for the treatment of these conditions, which are generally perceived as safer than plasma-derived blood products that have traditionally been used. Two articles this month consider issues related to pharmaceutical productivity. Kola and Landis look at the fiscal pressures that face the industry from the perspective of R&D and explore how we can improve on the current reduced R&D productivity, whereas Ashburn and Thor describe the strategy of repositioning existing drugs for new indications as a way of delivering productivity increases, and present a number of success stories. Recent success in another area — lead discovery — is highlighted in the review by Rees and colleagues, which focuses on approaches that involve the selection, screening and optimization of low-molecular-mass 'fragments', which offer a number of attractive features compared with traditional high-throughput screening. The reviews section is completed by Shi and Burn's comprehensive summary of the main enzymes that are involved in different stages of lipid homeostasis that might provide promising targets for the development of anti-obesity drugs.