Despite widespread distribution in most mammalian cells, the role of soluble guanylate cyclase has, until recently, been poorly defined, especially when compared with its more illustrious sibling, adenylate cyclase. In this review Adrian Hobbs outlines some of the reasons why the soluble guanylate cyclase-cGMP pathway has remained outside the signalling spotlight for much of the past 30 years. He goes on to describe how new molecular biological and biochemical approaches have facilitated a characterization of soluble guanylate cyclase and how this enzyme has acquired a profound physiological significance, and much research attention, as the intracellular 'receptor' for nitric oxide.