Anticoagulant therapy for the typical venous thromboembolism patient is straightforward with predictably favorable outcomes. However, for certain patients with venous thromboembolism, there remains uncertainty and controversy about optimal treatment. These controversial areas include venous thromboembolism patients with: heparin resistance, renal insufficiency, morbid obesity, cancer, antiphospholipid antibody syndrome, recurrent thrombosis despite appropriate anticoagulation, and patients with unprovoked VTE who may or may not benefit from thrombophilia testing. This review summarizes the current data for these special patient populations with venous thromboembolism and provides our recommendations for management.