Most surgeons, ourselves including, use retrograde cardioplegia in numerable operations in cardiac surgery. It is believed to be not only supplementary to antegrade, but also a unique alternative in special complicated cases. Regarding CABGs (coronary artery bypass grafts), many authors advocate its routine use together with antegrade, while others do not suggest it for standard practice. The existing disagreement on this special item is consequential to the different results among various protocols which have studied the effect of antegrade and retrograde perfusion. In these studies, fundamental variations in design, materials, and methods have resulted in an inability to compare results. Additionally, most of the published protocols studying cardioplegic arrest offer only a gross estimation of the microcirculatory perfusion, which is the basis of myocardial protection. Our present review is an attempt to elucidate the differences, explain the necessity of comparing retrograde cardioplegia alone with antegrade in CABGs for the reproduction of safe results, clarify the role of Thebesian veins and venovenous connections during retroperfusion, consider the critical anatomic differences between human hearts and those of animals which may result in serious study bias, and, finally, offer an explanation of what may really be going on in the microcirculation during antegrade and retrograde perfusion using a human capillary model.