Oral anticoagulation has proven to reduce mortality and morbidity of thromboembolic events. One of the most important determinants of the effectiveness and safety of anticoagulation therapy is the adherence to the prescribed therapy. Vitamin K antagonists are characterized by under-utilization, a narrow therapeutic window and multiple food and drug interactions which contribute to a variable dose-response relationship with the risk of insufficient protection and/or increased bleeding risk. The "new" direct oral anticoagulants have demonstrated equal or superior protection and reduced bleeding risks compared to warfarin and are easier to use because of fixed dosing without monitoring of anticoagulation. Controlling of adherence to the direct oral anticoagulants is difficult. Therefore, continuous and regular medication intake represents a pre-requisite for achieving optimal protection. The present review aims to give an overview about the factors that affect drug adherence in patients taking oral anticoagulation drugs and discusses strategies to improve drug adherence.