After a brief history of the main discoveries concerning the research on arachidonic acid and its biologically active derivatives, recent findings related to the identification of 2 isoenzymes of the prostaglandin-H synthase (PGHS) are reviewed. These isoenzymes play different roles within the body, since PGHS-1 is involved in homeostasis when PGHS-2 is mainly expressed during the inflammatory reaction. Non-steroidal anti-inflammatory drugs classically inhibit the biosynthesis of prostaglandins but this inhibitory effect depends on the considered isoenzyme. This discovery may have pharmacological and clinical impact but, at the present time, research is focused more on new pharmacological targets than on improving drug prescription.