The past year has seen many successful applications of a novel genetic approach — genome-wide association (GWA) — for identifying common genetic variants associated with complex diseases. In their Review, Kingsmore and colleagues highlight some of these successes, and consider the potential of GWA studies to provide novel therapeutic targets and genetic biomarkers for complex diseases including cancer and diabetes. Other complex disorders include those of the upper gastrointestinal tract, and Sanger and Lee discuss how developing drugs to modulate hormonal and neuronal aspects of the gut–brain axis, rather than targeting a single pathway, might be a more effective treatment strategy. In the Perspective this month, Kell and Dobson discuss evidence to support their proposal that the active uptake of drugs by membrane transporters is more common than has typically been assumed, and the implications for drug discovery and development. Membrane transporters have already proved to be attractive targets for prodrug strategies to improve the cellular uptake of active pharmacological agents. In this case, prodrugs — chemically modified versions of a compound that are converted to the active drug in vivo — can be designed to have structural features to promote their active uptake by endogenous transporters in the intestinal endothelium. Rautio and colleagues review common functional groups that are amenable to prodrug design, and highlight the application of the prodrug strategy for improving drug attributes including delivery, selectivity, efficacy and safety. Finally, in their Review, Smyth and colleagues discuss the potential of the cytokine interleukin 21 as a cancer immunotherapy, emphasizing how combination with agents including other immunotherapies, tumour-targeted antibodies, cytostatics or tyrosine kinase inhibitors could enhance antitumour efficacy.