Drug discovery covers an enormously wide spectrum of fields, and, in each issue of Nature Reviews Drug Discovery, we aim to target a selection of these, summarizing the essential developments in an authoritative and accessible form. This month, our articles focus on receptor theory, basic disease mechanisms, drug metabolism, drug delivery, new indications for existing drugs and animal experimentation. Terry Kenakin opens our Review section with a consideration of the meaning of efficacy, concluding that many rejected lead compounds might, in fact, have efficacies that go undetected due to the use of insufficiently sensitive screening assays. John Reed's summary of the expanding world of apoptosis-based therapies is complemented by this month's From the Analyst's Couch feature, which considers the emerging market for apoptosis-based anticancer drugs. Margaret Cascieri weighs the evidence for targeting the inflammatory process in atherosclerosis, a disease for which new therapeutic approaches are urgently required. William Pardridge tackles the substantial problem of how to slip drugs past the Berlin Wall that is the blood–brain barrier. In the last review, Lever and Page reveal the wide range of diseases for which heparin, once known just as an anticoagulant, now seems to be a promising new therapy. In the first of the Perspectives, Mark Matfield's Science and Society article draws attention to the role that scientists need to play in the public debate over the necessity of animal experimentation. Finally, we introduce the first in a series of Innovation articles describing novel technologies that have the potential to revolutionize drug discovery, in which Jeremy Nicholson and colleagues show how NMR can be used to monitor metabolite concentrations in plasma.