Deep vein thrombosis (DVT) is a common disease associated with high rates of mortality and significant morbidity. The diagnostic approach of DVT has evolved over the years. Algorithmical use of pretest probability, D-Dimer testing and ultrasonography allow safe and accurate investigation of DVT. The anticoagulation therapy, used to treat DVT, includes vitamin K antagonists (VKAs) and low-molecular-weight heparin (LMWH) or unfractionated heparin (UF). The duration of anticoagulation therapy depends on the cause of DVT and patient's clinical profile. Although these conventional therapies are effective, narrow therapeutic index, need for frequent monitoring and various food-drug interactions cause difficulties for patients. In recent decades, new oral anticoagulants have been developed. These drugs focus directly on inhibiting either Factor Xa (rivaroxaban, apixaban, edoxaban) or thrombin (dabigatran). In contrast to warfarin, these new agents have shorter half-life, fewer drug or food interactions, no necessity for a close monitoring and ease of administration. This review summarizes current knowledge about deep vein thrombosis and new treatment aspects with novel oral anticoagulants.