The p38 kinase plays a central role in inflammation, and it has been the subject of extensive efforts in both basic research and drug discovery. This review summarizes the biology of the p38 kinase with a focus on its role in inflammation. The p38 kinase regulates the production of key inflammatory mediators, including TNFα, IL-1β, and COX- 2. In addition, p38 also acts downstream of cytokines such as TNFα, mediating some of their effects. The potential efficacy of p38 inhibitors may thus be greater than would be expected from the inhibition of the mediators alone. Inhibitors of p38 kinase are currently in development for the treatment of rheumatoid arthritis. The biological processes regulated by p38 kinase suggest a wide variety of additional potential indications.