Soluble guanylate cyclase (sGC) is a heterodimeric haemoprotein, which represents the intracellular receptor for the ubiquitous biological messenger nitric oxide (NO). Activation of the enzyme facilitates conversion of GTP to the intracellular second messenger cGMP, and it is this molecule which mediates the majority of biological actions attributed to NO. sGC is expressed in virtually all mammalian cells and is important in mediating numerous physiological processes, including vascular and non-vascular smooth muscle relaxation, peripheral and central neurotransmission, platelet reactivity and phototransduction. Due to its ubiquitous nature, the pathogenesis of various disease states has been linked to aberrations in sGC signalling. This is especially true of the cardiovascular system, where inappropriate activation of sGC may underlie conditions such as stroke, atherosclerosis, impotence and septic shock; however, altered sGC activation has also been associated with the pathogenesis of asthma and certain neurodegenerative disorders. Therefore, agents that can modulate sGC function selectively will have considerable therapeutic potential, particularly in the treatment of cardiovascular disease.