Edema is a common morbidity following cardiopulmonary bypass (CPB) and can result in injury to many organs, including the heart, lungs, and brain. Generalized edema is also common and can lead to increased post-operative hospital stay and other morbidities. Pediatric patients are more susceptible to post-CPB edema and the consequences are more severe for this population. Hemodilution and systemic inflammatory responses are two suspected causes of CPB-related edema; however, the mechanisms involved are far from understood. Also, the common strategies to improve edema have not been completely successful and there is a need for new strategies at maintaining a fluid balance of patients as close to physiological as possible, especially for pediatric patients. An integrative approach to understanding edema is necessary as the forces involved in fluid homeostasis are dynamic and interdependent. Therefore, this review will focus on the physiology of fluid homeostasis and the pathologies of fluid shifts during CPB which lead to general edema as well as tissue-specific edema.