Phosphodiesterase is a ubiquitous enzyme that catalyses the hydrolysis of phosphodiester bonds. It is responsible for the hydrolysis of cyclic 3,5 adenosine monophosphate (cAMP) and 3,5 cyclic guanosine monophosphate (cGMP). Both cAMP, and to a lesser extent cGMP, have an important role in the regulation of inotropic mechanisms in the human myocardium. However, cAMP has numerous effects in other tissues, and different phosphodiesterase iso-enzymes are found in many other tissues (Table 1). Drugs which inhibit the action of phosphodiesterase (thus reducing the breakdown of cAMP) have a therapeutic action on the heart, lung, and vasculature as well as on platelet function and inflammatory mechanisms. Many of these drugs affect more than one isoenzyme, and many tissues have more than one iso-enzyme present. As a result, phosphodiesterase inhibitors (PDEI) can have a multiplicity of effects. For example, theophylline has effects on the lung, as well as cardiac and vascular effects; amrinone affects cardiac, vascular, and platelet functions. Sildenafil (Viagra) was originally studied as a possible anti-anginal agent. This review will concentrate on the effects of PDEI in cardiac and vascular tissue, primarily on their usefulness in the management of acute and chronic heart failure.