Looking back over the first 1,000 editorial pages of Nature Reviews Drug Discovery, we hope that we have been successful in our aim of covering all the stages of drug discovery and development. In this issue, Butte discusses the use and analysis of microarray data, which are having an increasingly important role in drug discovery; for example, in target identification. Dual-specificity protein phosphatases represent promising targets for the treatment of cancer, and Wipf, Lazo and colleagues provide the first comprehensive overview of the development of small-molecule inhibitors of these enzymes. Further down the pipeline are compounds that reduce nitric oxide synthesis, reviewed by Vallance and Leiper, which have the potential to treat several disease states, and which are soon to enter clinical trials. Microbicides that can block infection by HIV in the laboratory will also be evaluated in the clinic soon, as highlighted by Stone. And in the last Review, Remuzzi and colleagues summarize clinical results with endothelin antagonists — for which human trials have been less successful than anticipated on the basis of highly promising preclinical studies — and discuss possible approaches to maximizing their therapeutic potential. The Perspectives section features two articles that emphasize the value of a historical viewpoint in planning for the future. Shorter looks at the special circumstances surrounding the Drug Efficacy Review conducted in 1966–1968, which resulted in the withdrawal of almost half of the US psychopharmacopoeia, and proposes that some of these compounds might merit a re-appraisal. Finally, Miller, the leader of the FDA evaluation team that approved recombinant insulin, the first biotech drug, in 1982, considers the prospects for the biotech industry 20 years on.