Identifying a single factor that is common to the multiple clinical features of the metabolic syndrome, such as obesity and insulin resistance, might facilitate the development of an effective monotherapy. Ruderman and Prentki explore this concept by investigating the hypothesis that dysregulation of AMP kinase/malonyl-CoA signalling is central to this syndrome. The opposite of this 'magic bullet' approach for the management of mood disorders and schizophrenia is advocated by Roth and colleagues, who suggest that targeting several molecules is the best approach here. Braddock and Quinn review progress in the search for agents that modulate the activity of the cytokine interleukin-1 for the control of inflammatory diseases, such as rheumatoid arthritis. Targeting protein–protein interactions, such as those between cytokines and their receptors, with small molecules is generally viewed as highly challenging, but significant progress has been made in this endeavour recently, as highlighted by Arkin and Wells. Dorsett and Tuschl summarize the use of small interfering RNAs as gene silencing tools in functional genomics, and their potential as therapeutics, whereas the impact of gene patenting on biomedical research is evaluated by Stott and Valentine. Concerns about the current regulatory requirements are addressed in two articles. Rawlins argues that these requirements should be critically examined with a view to making changes that might address the rapidly growing costs of drug development. And one regulatory initiative, the FDA's Fast Track programme, is discussed in 'From the Analyst's Couch', which assesses the effects that Fast Track designation has on the speed of drug approval. Finally, two recently approved inhibitors of phosphodiesterase 5 for erectile dysfunction — tadalafil and vardenafil hydrochloride — are the subject of 'Fresh from the pipeline'.