Nitric oxide is a highly reactive free radical gas that has been implicated in a growing array of physiological and pathophysiological states. This signaling molecule represents a common component of the transduction pathways of a number of neurotransmitters that act via binding to G protein-coupled receptors, and an intense research effort into the elucidation of its molecular mechanisms of action is currently underway. The extreme lability of this substance necessitates a tight degree of nitric oxide regulation that is required in order to maintain appropriate cellular homeostasis. This review discusses some of the inter- and intracellular roles of nitric oxide, particularly with regard to their relationship to G protein-coupled receptor activation.