Portal vein thrombosis is a condition not infrequently encountered by clinicians. It results from a combination of local and systemic prothrombotic risk factors. The presentation of acute thrombosis varies widely from an asymptomatic state to presence of life-threatening intestinal ischemia and infarction. In the chronic stage, patients typically present with variceal bleeding or other complications of portal hypertension. Abdominal ultrasound color Doppler imaging has a 98% negative predictive value, and is considered the imaging modality of choice in diagnosing portal vein thrombosis. Controlled clinical trials to assist with clinical decision-making are lacking in both acute and chronic portal vein thrombosis. Oral anticoagulant therapy is initiated if the risks of bleeding are low, but long-term anticoagulation is generally not recommended in patients with concomitant hepatic cirrhosis. The roles of invasive therapeutic approaches such as thrombolysis and transjugular intrahepatic portosystemic shunt continue to evolve. This review conflates dissenting views into a rational approach of managing patients with portal vein thrombosis for the general internist.