The no reflow phenomenon can happen during elective or primary percutaneous coronary intervention. This phenomenon is thought to be a complex process involving multiple factors that eventually lead to microvascular obstruction and endothelial disruption. Key pathogenic components include distal atherothrombotic embolization, ischemic injury, reperfusion injury, and susceptibility of coronary microcirculation to injury. Thus, pharmacologic and mechanical strategies to prevent and treat no reflow target these mechanisms. Specifically, pharmacologic therapy consisting of vasodilators and antiplatelet agents have shown benefit in the treatment of no-reflow and mechanical therapies such as distal protection and aspiration thrombectomy have also shown benefit.