Background: Despite the survival benefit of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for treatment of refractory cardiogenic shock, it can also have potentially deleterious effects of left ventricular overload and pulmonary edema. The objective of this review was to investigate the current evidence on the incidence, diagnosis, risk factors, prevention, and interventions for left ventricular overload in adult and pediatric VA-ECMO patients. Methods: Five electronic databases, including MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews, were searched for original published studies from their dates of inception to January 2018. All types of adult and pediatric studies that investigated LV overload in VA-ECMO and were published in the English language were reviewed. Exclusion criteria included abstracts and conference presentations. Results: The reported incidence and sequelae of LV overload in VA-ECMO are highly variable, with presentations ranging from pulmonary arterial diastolic pressures of greater than 25 mmHg and LV distention on echocardiography, to severe pulmonary edema, LV thrombosis, and refractory ventricular arrhythmias. Currently, there are no standardized diagnostic criteria or guidelines for the type and timing of intervention for LV overload. Techniques for LV decompression have included direct surgical LV venting with catheter insertion via sternotomy or a minimally invasive incision; percutaneous catheterization via a transaortic, transseptal, or transpulmonary approach; ventricular assist devices; and intra-aortic balloon pumps. Conclusions: Left ventricular volume distention is a significant problem in VA-ECMO patients, with sequelae including myocardial ischemia, severe pulmonary edema, and intracardiac thrombosis. Further research is required on its incidence, diagnostic criteria, and risk factors, as well as the optimal timing and method for LV decompression, given the diversity of surgical and percutaneous techniques that are available.