Venous thrombosis results from the convergence of vessel wall injury and/or venous stasis, known as local triggering factors, and the occurrence of acquired and/or inherited thrombophilia, also known as systemic prothrombotic risk factors. Portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS) are caused by thrombosis and/or obstruction of the extrahepatic portal veins and the hepatic venous outflow tract, respectively. Several divergent prothrombotic disorders may underlie these distinct forms of large vessel thrombosis. While cirrhotic PVT is relatively common, especially in advanced liver disease, noncirrhotic and nontumoral PVT is rare and BCS is of intermediate incidence. In this article, we review pathogenic mechanisms and current concepts of patient management.