Scientists working in the field of cyclooxygenase enzymes have witnessed several major advances in the past two years. Crystal structures of fatty acid substrate and prostaglandin product complexes have been elucidated. Elegant site-directed mutagenesis studies have pinpointed the roles of key amino acids within the active site. Together, these results have provided key insights into the overall reaction mechanism. Detailed kinetics, spectroscopic and crystallographic studies have shed new light on the complex mechanism of inhibition of these fascinating enzymes. Finally, novel substrates of cyclooxygenase-2 have been identified.