This review explores the current literature on the natural history, diagnosis, and management of mesenteric venous thrombosis (MVT) in the modern era.A review of the contemporary literature from 1997 to 2016 on MVT and its pathogenesis, diagnosis, and treatment was performed.MVT is an insidious and lethal disease associated with acute mesenteric ischemia. The prevalence of MVT has increased sharply during the past two decades commensurate with an increase in radiographic imaging for abdominal complaints. The optimal treatment of and approach to MVT is controversial, given the poorly understood natural history of this rare disease. Both endovascular and open surgical strategies in addition to systemic anticoagulation have been used as adjuncts to treat MVT with limited success. Despite advances in treatment, mortality associated with MVT is still high. Furthermore, recent studies have shown that failure to recanalize the portomesenteric venous system leads to an increased risk for development of sequelae of portal hypertension.MVT is a challenging disease to treat, given the difficulty in establishing a prompt initial diagnosis and the inability to reliably monitor patients for evidence of impending bowel infarction. Careful selection of patients for endovascular, open, or hybrid approaches is key to achieving improved outcomes. However, the paucity of prospective data and our evolving understanding of the natural history of MVT make consensus treatment strategies difficult to ascertain.