Acute mesenteric ischemia (AMI) is a highly-lethal surgical emergency. Several pathophysiologic events (arterial obstruction, venous thrombosis and diffuse vasospasm) lead to a sudden decrease in mesenteric blood flow. Ischemia/reperfusion syndrome of the intestine is responsible for systemic abnormalities, leading to multi-organ failure and death. Early diagnosis is difficult because the clinical presentation is subtle, and the biological and radiological diagnostic tools lack sensitivity and specificity. Therapeutic options vary from conservative resuscitation, medical treatment, endovascular techniques and surgical resection and revascularization. A high index of suspicion is required for diagnosis, and prompt treatment is the only hope of reducing the mortality rate. Studies are in progress to provide more accurate diagnostic tools for early diagnosis. AMI can complicate the post-operative course of patients following cardio-pulmonary bypass (CPB). Several factors contribute to the systemic hypo-perfusion state, which is the most frequent pathophysiologic event. In this particular setting, the clinical presentation of AMI can be misleading, while the laboratory and radiological diagnostic tests often produce inconclusive results. The management strategies are controversial, but early treatment is critical for saving lives. Based on the experience of our team, we consider prompt exploratory laparotomy, irrespective of the results of the diagnostic tests, is the only way to provide objective assessment and adequate treatment, leading to dramatic reduction in the mortality rate.