If the benefits of antiplatelet and anticoagulant therapies are well established, bleeding complications appear underestimated in trials in comparison to their real-life incidence. Also, a large number of patients receive various associations of antiplatelet or anticoagulant treatments, while the benefit of some associations is not firmly established and data about their safety are missing. Identifying patients at high risk of bleeding is essential to define appropriate strategies. In this article we discuss the risk-benefit of various antiplatelet and anticoagulant molecules taken individually or in combination. An overview of the main clinical scores available to stratify the risk of bleeding is presented.