Cardiac surgery patients are potentially exposed to an acute inflammatory host response with a huge release of both pro- and anti-inflammatory cytokines both through intrinsic (e.g., tissue damage, endothelial injury) and extrinsic (e.g., anesthesia, extracorporeal circuits) mechanisms. Current standard of care therapy includes several invasive supportive treatments such as mechanical ventilation, continuous renal replacement therapy, ECMO, and/or cardiopulmonary bypass which may be responsible for an important inflammatory response. The inflammatory cytokine levels and hemodynamic status following these artificial treatments along with the current standard therapy are not always well controlled and may lead to worsened acute clinical conditions with prolonged in-hospital length of stay and increased mortality. In these settings, the administration of hemadsorption therapy with CytoSorb® has been supported by the successful results in several clinical studies as it has shown improvement of both the inflammatory profile and the hemodynamic vascular status of the patients. Therefore, in this narrative review, we summarized and discussed the current scientific literature on the role of CytoSorb^® treatment in case of cardiac surgery. According to the current evidences, the raised inflammatory levels and both inotropic and vasopressor requests in cardiac surgery patients need more tailored therapies and, in this contest, the hemadsorption with CytoSorb^® could play a pivotal role, especially on heart transplant patients. Furthermore, CytoSorb is currently the only hemadsorption sorbent authorized and efficiently applied for removing anticoagulant agents such as ticagrelor or rivaroxaban in patients undergoing cardiac surgery, to reduce perioperative bleeding complications and should be considered in high-risk patients.