Inflammatory diseases are a major burden on humanity, despite recent successes with biopharmaceuticals. Lack of responsiveness and resistance to these drugs, delivery problems and cost of manufacture of biopharmaceuticals mean that the search for new anti-inflammatory agents continues. Progress in our understanding of inflammatory signalling pathways has identified new targets, notably in pathways involving NF-kappaB, p38 MAP kinase, T lymphocyte activation and JAK/STAT. Other targets such as transcription factor complexes and components of pathways activated by TNF, Toll-like receptors and Nod-like receptors also present possibilities, and might show efficacy without being limited by effects on host defence. The challenge is to place a value on one target relative to another, and to devise strategies to modulate them.