Bleeding is an important issue in cardiothoracic surgery, and about 20% of all blood products are transfused in this clinical setting worldwide. Transfusion practices, however, are highly variable among different hospitals and more than 25% of allogeneic blood transfusions have been considered inappropriate. Furthermore, both bleeding and allogeneic blood transfusion are associated with increased morbidity, mortality, and hospital costs. In the past decades, several attempts have been made to find a universal hemostatic agent to ensure hemostasis during and after cardiothoracic surgery. Most drugs studied in this context have either failed to reduce bleeding and transfusion requirements or were associated with severe adverse events, such as acute renal failure or thrombotic/thromboembolic events and, in some cases, increased mortality. Therefore, an individualized goal-directed hemostatic therapy ("theranostic" approach) seems to be more appropriate to stop bleeding in this complex clinical setting. The use of point-of-care (POC) transfusion and coagulation management algorithms guided by viscoelastic tests such as thromboelastometry/thromboelastography in combination with POC platelet function tests such as whole blood impedance aggregometry, and based on first-line therapy with fibrinogen and prothrombin complex concentrate have been associated with reduced allogeneic blood transfusion requirements, reduced incidence of thrombotic/thromboembolic and transfusion-related adverse events, and improved outcomes in cardiac surgery. This article reviews the current literature dealing with the management of hemorrhage in cardiothoracic surgery based on POC diagnostics and with specific coagulation factor concentrates and its impact on transfusion requirements and patients' outcomes.