Looking back over past successes can be a rewarding exercise, and February sees the second in our series of 'Case Histories', in which Lars Olbe and colleagues review the programmes that led to the development of omeprazole — the best-selling drug in the world in the late 1990s — and its successor esomeprazole. A more recent success is highlighted in this month's 'Fresh from the pipeline', which focuses on ezetimibe, a newly launched cholesterol-lowering drug with a novel mechanism of action. Heart failure is the leading cause of death in industrialized nations, and the lead review, by Chris Vlahos and colleagues, assesses the possibility of targeting kinases as therapeutic candidates for heart disease. David Davies reviews our current understanding of resistance to antibiotics by bacterial biofilms — organized structures that may account for over 80% of infections. The two remaining reviews in this issue focus on technologies. Markus Rudin and Ralph Weissleder highlight how recent advances in molecular imaging are now extending the applications of imaging techniques from their traditional use in the clinic to earlier stages in drug discovery. Gary Glish and Richard Vachet provide an accessible summary of the principles of mass spectrometry. This month's 'From the Analyst's Couch' summarizes the new molecular entities approved by regulatory authorities in the United States and Europe in 2002. In the light of the worryingly low totals of new drugs, David Horrobin's questioning of the validity of the standard use of in vitro and in vivo models in biomedical research in his 'Guide to Drug Discovery' article takes on a particular significance. Finally, Chris Dobson gives an overview of the inaugural Horizon Symposium on 'Protein folding and disease'.