Dipyridamole stress is the forerunner and prototype of pharmacological stress echo tests in the diagnosis of coronary artery disease. The safety of this test has been conclusively demonstrated as a result of extensive experience in large-scale multicenter projects. The diagnostic accuracy of dipyridamole stress echo is comparable to dobutamine and largely a function of the employed dose. Higher dosages (up to 0.84 mg/kg) are being required to achieve good sensitivity. The prognostic value has been shown to be independent and additive to clinical, exercise echocardiogram, and angiographic data. The test positive response should be titrated on the basis of severity, extent, and timing of induced dyssynergy with low positivity being associated to more anatomically and functionally severe forms of disease. Multicenter, randomized, prospective, international studies on cost-effectiveness directly comparing a noninvasive strategy centered on stress echo versus an invasive strategy centered on coronary angiography are currently ongoing.