Dual antiplatelet therapy is currently recommended for all patients with acute coronary syndromes, independent of whether they receive pharmacological treatment or undergo percutaneous coronary intervention. Antiplatelet agents are the cornerstone of pharmacological treatment in interventional cardiology. However, there is a clear need for randomized trials to assess the treatment strategy of dual antiplatelet therapy in patients who also need long-term antithrombotic treatment (such as those with atrial fibrillation, prosthetic heart valve, mitral valve regurgitation or stenosis, deep vein thrombosis, pulmonary embolism, or pulmonary hypertension). In this paper we discuss trials and analyses on the use of dual antiplatelet treatment in combination with antithrombotic therapy in particular diseases, with a focus on the risk of hemorrhagic events connected with this treatment, as well as recent guidelines of the European Society of Cardiology, the American College of Cardiology, and the American Heart Association.