Microvascular perfusion is considered a key factor with respect to preservation of left ventricular function and prognosis. No-reflow is recognised in the context of acute coronary syndromes and percutaneous intervention: myocardial blood flow at a tissue level remains impaired following restoration of epicardial flow. Once no-reflow is established, treatment is often ineffective and this phenomenon is associated with poor short- and long-term outcomes. A number of different pharmacological agents are used to prevent and treat this condition although data to support their use are limited. This article examines the pathophysiological aspects of this condition, its clinical correlates and proposed management strategies.