Without doubt, evolution of cardiopulmonary bypass (CPB) in the second half of the twentieth century was the most important step in the advancement of cardiac surgery, allowing surgeons to perform complex procedures on a still and bloodless heart while maintaining the systemic perfusion and oxygenation. A combination of mechanical and biological components is carefully designed to form the CPB circuit. Although CPB properly performs the role of both heart and lung during surgery, it is a non-physiologic state and induces a wide spectrum of inflammatory response and pathologic changes in nearly all organs. These changes are insignificant in the presence of the adequate physiologic reserve in most patients. With growing technology, future innovations will likely focus on enhancing more biocompatible CPB circuit and integrating artificial intelligent for monitoring systems. Understanding the components and tasks of the CPB circuit is essential for healthcare professionals to anticipate and manage potential complications. This chapter provides an overview of the structures in CPB circuit and function of each component in the first section. In the second section, clinical considerations as well as strategies to minimize related complications and recovery improvement are reviewed.