Advanced chronic liver disease is frequently accompanied by thrombocytopenia and ill-defined platelet function defects. The cause for thrombocytopenia in these patients is multifactorial and includes platelet sequestration in an enlarged spleen, platelet consumption related to low-grade activation of coagulation, decreased platelet production due to decreased hepatic production of thrombopoietin and direct toxic effects of disease-causing agents or drugs on the bone marrow, and increased clearance, in part related to autoantibodies. Platelet function disorders in patients with advanced liver disease have been poorly characterized, which in part relates to the difficulty of performing platelet function tests in thrombocytopenic blood. The reduced platelet count in these patients is, at least partly, compensated for by highly elevated levels of the platelet adhesive protein von Willebrand factor. Consequently, severe bleeding as a direct result of thrombocytopenia is uncommon and contemporary clinical guidance documents argue against measures such as platelet concentrate transfusions or administration of thrombopoietin receptor agonists to increase the platelet count to avoid spontaneous or procedure-related bleeding in these patients. A subgroup of very ill patients may benefit from such interventions, and studies identifying patients that may benefit are required. Patients with advanced chronic liver disease may also require platelet function inhibitory drugs, for example, for the management of arterial thrombotic events, but the use of such agents is complicated by the frequent thrombocytopenia and associated fear of antiplatelet drug-induced bleeding.