Nitric oxide synthase and cyclooxygenase pathways share a number of similarities. NOS produces nitric oxide (NO) and COX generates prostaglandins. Two major forms of NOS and COX have been discovered to date: constitutive versus inducible forms. The constitutive forms play a role in housekeeping and physiological states, while the inducible forms are overexpressed under pathological conditions such as inflammation in a variety of cells, producing a large amount of NO or prostaglandins. The cross talk between the COX and NOS pathways was initially reported in 1993 when they demonstrated in a series of in vitro and in vivo studies that NO activates the COX enzymes to produce increased amounts of prostaglandins. Those studies led to the concept that COX enzymes represent important endogenous "receptor" targets for amplifying or modulating the multifaceted roles of NO in physiology and pathology. Since then, numerous studies have been undertaken to delineate the functional consequences of this interaction as well as the potential mechanism by which each pathway interacts. This review focuses in particular on recent advances in this field that extend our understanding of these two pathways under various systems.