Retrograde coronary venous perfusion can preserve myocardium during experimental coronary artery occlusion and has been used clinically to deliver oxygenated blood to ischemic myocardium during unstable angina or high-risk percutaneous transluminal coronary angioplasty (PTCA). Retrograde delivery of drugs accelerates coronary thrombolysis, preserves regional myocardial function, and limits infarct size in animal models. Modifications of the coronary venous retroperfusion technique have allowed access to smaller coronary venous branches and minimization of systemic effects of local drug delivery. Retrograde coronary sinus perfusion as an adjunct in high-risk coronary PTCA is limited by its inability to provide systemic hemodynamic support during circulatory collapse. Targeted and specific gene delivery to myocardium with transfection rates superior to intraarterial or systemic injection may be a promising new application for this technique. The coronary venous system can also be used for the noninvasive creation of coronary artery bypasses or the insertion of leads for left ventricular pacing. Contrast-enhanced electron beam computed tomography (EBCT) can noninvasively provide high-resolution imaging of the coronary vessels with qualitative and quantitative information on coronary venous anatomy and coronary arteriovenous relationships and may help in selecting appropriate candidates, anticipating the degree of difficulty of the procedure, and guiding the approach. Therefore, EBCT may become the imaging modality of choice for the assessment of patients considered for such strategies.