Implementing normothermic regional perfusion (NRP) requires the use of an extracorporeal circuit to provide oxygen delivery, carbon dioxide removal, and temperature modulation. Its main components include drainage and return tubing, a blood pump, a membrane lung, and a heater-exchanger. Hybrid circuits may include a venous reservoir. The drainage limb of the circuit is connected to a venous cannula, while the return limb to an arterial cannula. The circuit is operated via a driving unit, which controls the motor, provides monitoring and safety features, depending on the device, and stores internal batteries. Basic and advanced monitoring is pivotal during NRP, as numerous complications may occur. Some of these are mechanical issues related to the circuit, while others are complex scenarios which could be related to the circuit, to the physiology of extracorporeal support, or to the complex interactions between the two during reperfusion. Any complications may negatively impact on the feasibility and on the effectiveness of NRP, so should be prevented, early detected, and promptly managed to improve the outcome.