Hot on the heels of December's publication of the mouse genome in Nature, this first Nature Reviews Drug Discovery of 2003 features a timely review from Brian Zambrowicz and Arthur Sands evaluating the role of mouse-knockout technology for target discovery and validation. The authors analyse the knockout phenotypes for targets of the top 100 best-selling drugs and give their predictions for the number of relevant drug targets we can expect to discover over the coming years. In a complementary article — the first in our 'Guide to drug discovery' series — Jonathan Knowles and Gianni Gromo provide an introduction to the key issues in target selection and discuss the rationale for decision-making when choosing targets. Biotechnology is one of the themes of this issue, and in a review focusing on nanotechnology, Charles Martin and Punit Kohli discuss the emerging field of nanotubes — nanostructures that have diverse uses in biomedical and biotechnological applications. Therapeutic antibodies are already commercially available to treat a variety of diseases, with more set to follow, and Ole Brekke and Inger Sandlie review the latest antibody technologies. As biotech turns 20, Kevin Pang and colleagues continue their analysis of what the next 20 years might hold for biotech-based drug development. In our lead review, Deepak Bhatt and Eric Topol summarize antiplatelet therapies for the treatment of cardiovascular disease and highlight novel targets for the inhibition of platelet function. Finally, in our lead Perspective, Justina Molzon takes a look at the Common Technical Document, the new face for the NDA, which is launched worldwide in 2003 and is set to become mandatory in Europe and Japan later this year.