AbstractMicrosomal prostaglandin E synthase‐1 (mPGES‐1) is an inducible terminal synthase in PGE2 biosynthesis by inflammatory and cancer cells. Clinical and experimental data emphasize that mPGES‐1 might be a valuable target, with improved selectivity and safety compared to traditional NSAIDs or selective COX‐2 inhibitors, in the treatment of inflammatory diseases, different types of cancer as well as central symptoms elicited by peripheral inflammation. Since the first characterization of mPGES‐1, the numbers of publications on mPGES‐1 structure, pathogenic role and inhibitor development have increased exponentially; however, there are currently no selective mPGES‐1 inhibitors available for clinical use. In this MiniReview, we focus on recent advances in the development of selective inhibitors of mPGES‐1 activity, with the aim to discuss the effects of targeting mPGES‐1 in different inflammatory models in vitro and in vivo.