Left ventricular assist devices (LVAD) are an increasingly implemented therapeutic intervention for patients with end-stage heart failure. A growing body of evidence, however, has shown an elevated risk of device thrombosis, a major complication jeopardizing the patient's post-implantation survival. To date, multiple causative factors for LVAD thrombosis have been identified, such as internal shear stress, device material, infection, and inadequate anticoagulation. Understanding the mechanisms leading to LVAD thrombosis will not only enable device optimization, but also allow for better patient handling, hence improving post-implantation outcome. In this review we highlight the most commonly identified factors leading to LVAD thrombosis and discuss their mechanisms.