External counterpulsation (ECP) was originally conceived to be a circulatory assist device to promote blood flow to areas of the heart muscle that were lacking adequate blood supply due to obstruction of the coronary artery. During ECP the lower extremities are compressed to squeeze both arterial and venous blood back to the heart during diastole, increasing coronary perfusion pressure and right ventricular filling. The compression is released during systole, effectively increasing peripheral arterial capacitance and thereby lowering impedance to cardiac ejection and systolic workload. Enhanced external counterpulsation (EECP) was designed in the late 1970s with three pneumatic cuffs wrapped around the calves, lower and upper thighs. These cuffs are inflated sequentially to increase the volume of peripheral blood that can be effectively pumped back towards the heart. During the last four decades EECP has been demonstrated to be clinically effective in the treatment of patients with coronary artery disease. However, beside the acute hemodynamic effects that can be readily observed during EECP treatment, its mechanisms of action and its long-term effects are less well established and have only been rigorously examined within the past five years. Theoretically, EECP treatment can provide benefit through enhanced recruitment of collateral circulation and a variety of peripheral vascular effects, including improved endothelial function. Collaterals are small vessels that supply arterial blood to ischemic myocardium distal to the obstructed artery. They are created by the increased pressure gradient across a vascular stenosis and by angiogenic factors released as a result of the vascular shear forces produced during EECP treatment. In fact the most promising and beneficial effects of EECP treatment may involve these measurable and reproducible peripheral and endothelial effects of EECP treatment and will be the primary focus of this review.