Oral anticoagulant therapy, either with vitamin K antagonists (VKAs) or with novel oral anticoagulants such as dabigatran, rivaroxaban, and apixaban, is the mainstay for thromboprophylaxis in patients with atrial fibrillation (AF). Thromboembolic risk factors associated with AF and risk factors for bleeding associated with oral anticoagulant therapy are largely the same, and bleeding risk very rarely outweighs individual benefit of thrombosis prevention, thus resulting in positive net clinical benefit of oral anticoagulant therapy in almost all AF patients. Prevention of AF‑related thromboembolic events most commonly requires long‑term oral anticoagulant therapy. Over time, various clinical situations may occur in a given patient (e.g., a need for an urgent surgery or invasive intervention, acute stroke, etc.), which may require a temporary or permanent modification of anticoagulant therapy regardless of which anticoagulant drug has been used. This may be particularly challenging for physicians because many issues regarding optimal use of oral anticoagulant drugs in specific clinical situations still remain to be solved. In this review article, we discuss the periprocedural management of oral anticoagulant therapy, bridging, transition to another oral anticoagulant, the occurrence of acute stroke in a patient already taking an oral anticoagulant, and decision when it is safe to resume oral anticoagulation therapy after stroke. We summarize the available evidence and current (and future) approaches to oral anticoagulation management in such clinical situations.