Direct oral anticoagulants (DOACs) are drugs that have been increasingly used for the prevention and treatment of tromboembolic diseases in the past decade. According to the mechanism of action, they are divided into two groups: 1. direct inhibitor of thrombin or activated coagulation factor II (FIia) that includes dabigatran (Pradaxa®, Boehringer Ingelheim) and 2. direct inhibitors of activated factor X (FXa) that include rivaroxaban (Xarelto®, Bayer), apixaban (Eliquis®, Pfizer) and edoxaban (Lixiana®, Daiichi-Sankyo). At present, ali four drugs are licensed for the prevention of venous thromboembolism (VTE) in patients undergoing orthopedic knee or hip replacement surgery, for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and for prevention and treatment of VTE including deep vein thrombosis (DVT) and noncomplicated pulmonary embolism (PE). These drugs have rapid onset and offset of action, more predictable pharmacokinetic and pharmacodynamic properties, equal or superior efficacy and improved safety for the patient compared to the vitamin K antagonists (VKAs) that have been used for decades as the only available oral anticoagulants. In contrast to VKAs, DOACs are administered in a fixed <lose and no routine coagulation monitoring is required for these drugs. However, despite of their advantages compared to VKAs, DOACs also have an increased risk of bleeding as the most important side effect of treatment. Although it is generally accepted view that clinical application of DOACs does not require frequent laboratory control because the medication dosage is not based on the results of laboratory tests, the results of first clinical experiences also dispute the fact that the treatment with DOACs completely excludes the need for laboratory diagnostics. The growing clinical experience with these drugs during several years strongly suggests that there are special clinical circumstances and patient populations in which laboratory measurement of DOACs should be performed, including bleeding or thromboembolic events, invasive diagnostic procedures or surgery, extremes of body weight and suspected 11011-compliance or overdose. Treatment of patients with DOACs has a significant impact on the results of commonly used screening coagulation assays i.e., prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). However, due to significant differences in the sensitivity of individual commercial reagents for these screening coagulation tests in relation to a particular DOAC drug, these assays are not appropriate for reliable assessment of their anticoagulant effect, but rather exclusively for rough estimation of the drug dosage in emergency situations of the life-threatening patients. Among screening coagulation assays, the result of PT test is influenced by FXa inhibitors, while dabigatran affects the results of APTT and TT assays. Knowing the impact of DOACs on the results of screening coagulation assays (PT, APTT, TT) is a precondition for the correct interpretation of the test results. With the introduction of DOACs in clinical practice, the major challenge in the field of laboratory medicine was to find and introduce appropriate methods for assessment of anticoagulant effects of these medications. Thus, simultaneously with the first clinical experiences in application of DOACs, research has also been focused on the development of specific coagulation methods that allow quantitative determination of concentration of these drugs. Coagulometric and chromogenic methods have been designed as quantitative methods for measuring the concentration of individual DOACs in plasma. Dabigatran concentrations can be determined by coagulometric methods (diluted TT and ecarin clotting time assays) as well as with the newer chromogenic methods (chromogenic ecarin assay and anti-Ila assay), whereas quantitative methods for determination the concentration of direct FXa inhibitors include exclusively chromogenic anti-Xa method using calibration with appropriate drug. These quantitative methods have been so far applied in research related to DOACs exclusively, but they only are becoming commercially available, and their implementation in specialized coagulation laboratories for now is still at the very beginning. lt is excepted that the application of specific quantitative methods for measuring the concentration of DOACs will be a great support and help in making clinical decisions in certain clinical situations. However, because many unknowns associated with the use of these drugs are still present, it is a long journey of research to enable DOACs to completely replace the old anticoagulants.