SonoVue is a second-generation ultrasound contrast agent consisting of phospholipid-stabilized microbubbles filled with sulfur hexafluoride, with outstanding stability and resistance to pressure. The efficacy of SonoVue (0.5, 1, 2, 4 mL) was compared with Albunex (doses 0.08 and 0.22 mL/kg) in patients with suspected ischemic disease and suboptimal endocardial-border delineation on unenhanced echocardiography at rest. All the doses resulted in significantly greater increases compared with Albunex in left-ventricular endocardial-border delineation score as well as in the duration of clinically useful contrast effect. The utility of SonoVue in diagnosing ischemic heart disease was also evaluated during pharmacologic stress (arbutamine or dobutamine). SonoVue produced significant increases from baseline in endocardial-border delineation score both at rest and during pharmacologic stress. The possibility of detecting myocardial perfusion defects using SonoVue-enhanced power Doppler and gray-scale harmonic contrast echocardiography associated with continuous and intermittent imaging was assessed in patients with coronary artery disease. The results obtained were comparable with corresponding 99mTc sestamibi single-photon emission computed tomography images. An effective cardiovascular assessment of a patient should also include the evaluation of carotid vessels, intracranial circulation, and renal arteries. SonoVue provided significant improvements in the evaluation of the Doppler signal in terms of diagnosis agreement with reference imaging modality especially for intracranial vessels. The safety profile of SonoVue was evaluated in 1,406 patients. The incidence of adverse events was 10.4%, the great majority of which were of mild intensity and resolved without consequences.