In this review, we analyze the epidemiology of thromboses related to end-stage liver disease (ESLD), discuss causes of hypercoagulability, describe susceptible populations, and critically evaluate proposed prophylaxis and treatment of thromboses. Classically, ESLD has been regarded as a model for coagulopathy, and patients were deemed to be at high risk for bleeding complications. Patients with ESLD are not auto-anticoagulated, and they do not have a lower risk of portal vein thrombosis, intracardiac thrombus formation, pulmonary embolism or hepatic artery thrombosis. Though the cause of hypercoagulability is multifactorial, endothelial dysfunction likely plays a central role for all patients with ESLD. Some subpopulations, such as patients with nonalcoholic steatohepatitis and autoimmune conditions, are at increased risk of thrombotic events as are patients of Hispanic ethnicity. The science behind prophylaxis of different types of clotting and treatment of thromboses is developing rapidly. A number of medications, including low molecular weight heparin, unfractionated heparin, aspirin, vitamin K antagonists, and direct oral anticoagulants can be used, but clear guidelines are lacking. Acute intraoperative clotting can be associated with high mortality. Routine use of transesophageal echocardiography can be helpful in early recognition and treatment of intraoperative thrombosis. Heparin should be reserved for cases of intracardiac thrombus/pulmonary embolism without hemodynamic instability. In unstable patients, low dose of recombinant tissue plasminogen activator can be used. In this new era of heightened awareness of thrombotic events in ESLD patients, prospective randomized trials are urgently needed to best guide clinical practice.