We have reviewed the role of nitric oxide synthase(NOS)isoforms and nitric oxide(NO)in the normal heart and in heart failure.NO is a highly reactive siganaling molecule produced normally in the heart and is an important modulator of myocardial function.NOS catalyzes the conversion of L-arginine to L-citrulline and NO.In the heart,three NOS isoforms are present:neuronal NOS(nNOS),and endothelial NOS(eNOS),are constitutively present enzymes in distinct subcellular locations within cardiomyocytes,whereas inducible NOS(iNOS)is absent in the healthy heart,but its expression is induced by inflammation and immune responses.In the tissue,NO has two main effects:(i)it stimulates the activity of guanylate cyclase,and(ii)nitrosylates tyrosine residues in proteins and thiol-groups of cysteine in proteins.Changes in subcellular compartmentalization of NOS isoforms lead to the increased NO synthesis,reduction of the specificity of its effects,disruption of calcium homeostasis,electromechanical uncoupling and myocardial contractile failure.