Mechanical circulatory support (MCS) is the overarching term that encompasses the temporary and durable devices used in patients with severe heart failure. MCS disturbs the hematologic and coagulation system, leading to platelet activation, activation of the contact pathway of coagulation, and acquired von Willebrand syndrome. Ischemic stroke and major hemorrhage occur in up to 30% of patients. Hematologists are an essential part of the MCS team because they understand the delicate balance between bleeding and clotting and alteration of hemostasis with antithrombotic therapy. However, prior to this important collaborative role, learning the terminology used in the field and types of MCS devices allows improved communication with the MCS team and best patient care. Understanding which antithromobotic therapies are used at baseline is also required to provide recommendations if hemorrhage or thrombosis occurs. Additional challenging consultations in MCS patients include the influence of thrombophilia on the risk for thrombosis and management of heparin-induced thrombocytopenia. This narrative review will provide a foundation to understand MCS devices how to prevent, diagnose, and manage MCS thrombosis for the practicing hematologist.