Ischemic stroke (IS) is a severe complication and leading cause of mortality in patients under extracorporeal membrane oxygenation (ECMO). The aim of our narrative review is to summarize the existing evidence and provide a deep examination of the diagnosis and treatment of acute ischemic stroke patients undergoing ECMO support. The incidence rate of ISs is estimated to be between 1 and 8%, while the mortality rate ranges from 44 to 76%, depending on several factors, including ECMO type, duration of support and patient characteristics. Several mechanisms leading to ISs during ECMO have been identified, with thromboembolic events and cerebral hypoperfusion being the most common causes. However, considering that most of the ECMO patients are severely ill or under sedation, stroke symptoms are often underdiagnosed. Multimodal monitoring and daily clinical assessment could be useful preventive techniques. Early recognition of neurological deficits is of paramount importance for prompt therapeutic interventions. All ECMO patients with suspected strokes should immediately receive brain computed tomography (CT) and CT angiography (CTA) for the identification of large vessel occlusion (LVO) and assessment of collateral blood flow. CT perfusion (CTP) can further assist in the detection of viable tissue (penumbra), especially in cases of strokes of unknown onset. Catheter angiography is required to confirm LVO detected on CTA. Intravenous thrombolytic therapy is usually contraindicated in ECMO as most patients are on active anticoagulation treatment. Therefore, mechanical thrombectomy is the preferred treatment option in cases where there is evidence of LVO. The choice of the arterial vascular access used to perform mechanical thrombectomy should be discussed between interventional radiologists and an ECMO team. Anticoagulation management during the acute phase of IS should be individualized after the thromboembolic risk has been carefully balanced against hemorrhagic risk. A multidisciplinary approach is essential for the optimal management of ISs in patients treated with ECMO.