The widespread introduction of direct oral anticoagulants (DOAC) represents a major step forward in the therapeutic management of patients with venous thromboembolic disease and atrial fibrillation, accompanied by new challenges. A thorough knowledge of the available evidence needs to be associated with pragmatism in order to address patients' individual issues. Access to documents containing practical guidance will certainly contribute to increase the efficacy and safety of prescription of these drugs for patients. The aim of this article is to present suggestions based on scientific data and international recommendations for the prescription and further management of DOACs in everyday clinical practice, based of frequently asked questions to the authors.