Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.