A continued need to develop safe and effective analgesics and anti-inflammatory drugs fuels the ongoing investigations of cyclooxygenase (COX). Since the early 1990s, it has been appreciated that there are two cyclooxygenase enzymes, cyclooxygenase-1 and cyclooxygenase-2, responsible for the production of prostaglandin H2, the first step in prostanoid biosynthesis. Cyclooxygenase-1 was responsible for the physiological production of prostanoids and cyclooxygenase- 2 was responsible for the elevated production of prostanoids that occurred in sites of disease and inflammation COX-3 is an enzyme that is encoded by the PTGS1 (COX1) gene and is the third and most recently discovered cyclooxygenase (COX) isozyme. The COX-3 isozyme is encoded by the same gene as COX-1, with the difference that COX-3 retains an intron that is not retained in COX-1. In dogs the resulting protein resembles the other two COX enzymes, but in mice and humans it does not, owing to a frame-shift mechanism. Key words: Cyclooxygenase, COX-3, Prostaglandins, Inflammation, NSAIDs