Introduction: Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients presenting acute cardiac and/or pulmonary dysfunctions, who are at high risk of developing acute kidney injury and fluid overload. Continuous renal replacement therapy (CRRT) is commonly used in intensive care units (ICU) to provide renal replacement and fluid management. We conducted a review to assess the feasibility, efficacy and safety of the combination of ECMO and CRRT and to illustrate the indications and methodology of providing renal replacement therapy during the ECMO procedure. Method: We searched for all published reports of a randomized controlled trial (RCT), quasi-RCT, or other comparative study design, conducted in patients undergoing ECMO plus CRRT. Two reviewers independently selected potential studies and extracted data. We used the modified Jadad scale and the Newcastle-Ottawa for quality assessment of RCTs and non-RCTs, respectively. Statistical analyses were performed using RevMan 5.2. Results: We identified 19 studies meeting the eligibility criteria (seven cohort, six case control, one historically controlled trial and five studies of technical aspects). There are three major methods for performing CRRT during ECMO: independent CRRT access, introduction of a hemofiltration filter into the ECMO circuit (in-line hemofilter) and introduction of a CRRT device into the ECMO circuit. We conducted a review with limited data synthesis rather than a formal meta-analysis because there could be greater heterogeneity in a systematic review of non-randomized studies than that of randomized trials. For ECMO survivors receiving CRRT, overall fluid balance was less than that in non-CRRT survivors. There was a higher mortality and a longer ECMO duration when CRRT was added, which may reflect a relatively higher severity of illness in patients who received ECMO plus CRRT. Conclusions: The combination of ECMO and CRRT in a variety of methods appears to be a safe and effective technique that improves fluid balance and electrolyte disturbances. Prospective studies would be beneficial in determining the potential of this technique to improve the outcome in critically ill patients.