This month we are delighted to be celebrating 10 years of Nature Reviews Drug Discovery (see the editorial on page 3). Reflecting our continuing aim to feature articles across the broad spectrum of areas relevant to drug discovery and development, our Review articles this month cover an array of topics. The threat of antibiotic resistance necessitates the development of improved drugs, and Schneider and colleagues present an emerging strategy based on the exploitation of naturally occurring host defence antimicrobial peptides (AMPs). They discuss how recent advances in computer-assisted peptide design strategies are enabling the creation of more potent, broad-spectrum AMPs that may lead to next-generation antibiotics. Meanwhile, Pommier and Marchand discuss the concept of interfacial inhibition, an effective approach for targeting complex macromolecular systems, which involves the selective binding of an agent to the interface of macromolecules within a complex undergoing a conformational change. Exemplified by antibiotic, antiviral and anticancer agents, they define the mechanisms of action of interfacial inhibitors and discuss the implications for future drug discovery. Cancer is one of a range of diseases in which serine hydrolases — a large and diverse class of enzymes — are therapeutic targets. Bachovchin and Cravatt focus on the therapeutic potential of the mammalian serine hydrolases, many of which are poorly characterized and lack selective chemical inhibitors, and describe strategies for the discovery of novel inhibitors. Finally, Hollenberg and colleagues summarize the activation and signalling mechanisms of the G protein-coupled proteinase-activated receptors, and discuss their potential as therapeutic targets in cardiovascular, musculoskeletal, gastrointestinal, respiratory and central nervous system disorders.