Inducible, glutathione-dependent microsomal prostaglandin E synthase (mPGES) catalyzes the formation of prostaglandin (PG) E2 from cyclooxygenase (COX) derived PGH2. There is a strong association between mPGES and COX-2 protein expression in various cells and tissues. The same types of proinflammatory stimuli induce both enzymes and they co-localize in the cells. In cancer, however, the expression of these two enzymes seems uncoordinated, a fact that should be considered when interpreting recent data from clinical trials testing nonsteroidal anti-inflammatory drugs (NSAIDs) as chemoprotectants against cancer. The importance of mPGES for induced PGE2 biosynthesis was recently demonstrated in mice lacking mPGES. This review intends to summarize briefly the data that have been published on mPGES and discuss the assumed pathophysiological roles of this enzyme in inflammation, atherosclerosis, cancer, and in centrally mediated responses to inflammation.