Weaning from cardiopulmonary bypass (CPB) requires the heart to resume its function as the driving force of blood flow, taking over from the mechanical pump in the CPB circuit. Weaning, the process of transition from CPB to physiological circulation, requires excellent communication and teamwork between the perfusionist, surgeon, and anesthetist. Cardiac function must be optimized prior to weaning from CPB to achieve a smooth transition. Delays in investigating or treating abnormal parameters may lead to the heart failing, necessitating a return to extracorporeal circulation. Consequently, anticipation of possible cardiac dysfunction and thorough advance preparation are key elements of the weaning process. This article aimed to mention the weaning process, difficulties, and management of CPB.