The main goal of this article is to update etiology, epidemiology, diagnosis, treatment and outcome of the various causes of mesenteric ischemia in order to elucidate its labyrinthine clinical riddle, by reviewing the current English medical literature. Mesenteric ischemia is a quite uncommon disorder, observed in the emergency department. It is a life-threatening vascular emergency that requires early diagnosis and intervention to restore mesenteric blood flow and to prevent bowel necrosis and patient death. Consequently, it is a vital diagnosis to make because of its high mortality rate and its thorny complications. The underlying causes vary, and the prognosis depends on the specific findings during clinical examination. Vague and nonspecific clinical findings and limitations of diagnostic studies make the diagnosis a significant challenge. The prognosis of acute mesenteric ischemia of any type is grave. The complications following this medical jigsaw puzzle are also severe. Patients in whom the diagnosis is missed until infarction occurs have a mortality rate of 90%. Even with good treatment, up to 50-80% of patients die. Survivors of extensive bowel resection face lifelong disability. Despite the progress in understanding the pathogenesis of mesenteric ischemia and the development of treatment modalities, the entity remains a diagnostic challenge for clinicians. Delay in diagnosis contributes to a high mortality rate. Early diagnosis and adequate treatment can improve the clinical outcome. Even if diagnostic modalities have improved since the first successful attempts to confront effectively this clinical entity, mesenteric ischemia still remains a lethal diagnostic enigma for the medical community.