Extracorporeal membrane oxygenation (ECMO) is a temporary life support system used to assist patients with life-threatening severe cardiac and/or respiratory insufficiency. Patients requiring ECMO can be considered the sickest patients admitted to the intensive care unit (ICU). Acute kidney injury (AKI) represents a frequent complication during ECMO, affecting up to 70% of patients, with multifactorial pathophysiology and an independent risk factor for mortality. Severe AKI requiring Continuous Renal Replacement Therapy (CRRT) occurs in 20% of ECMO patients, but multiple indications and different timing may imply a significantly higher application rate in different centers. CRRT can be run in parallel to ECMO through different vascular access, or it can be conducted in series by connecting the circuits. Anticoagulation of ECMO is typically managed with systemic heparin, but several approaches can be applied for the CRRT circuit, from no anticoagulation to the addition of intra-filter heparin or regional citrate anticoagulation. The combination of CRRT and ECMO can be considered a form of multiple organ support therapy, but this approach still requires optimization in timing, set-up, anticoagulation, prescription and delivery. The aim of this report is to review the pathophysiology of AKI, the CRRT delivery, anticoagulation strategies and outcomes of patients with AKI treated with ECMO.