Unilateral lung diseases such as unilateral pneumonia, trauma or pulmonary hemorrhage can cause profound hypoxemic respiratory failure necessitating mechanical ventilation. These disorders are characterized by marked asymmetry in lung mechanics, with the affected lung having a lower compliance compared to the healthier lung, and management involves complex strategies such as simultaneous independent lung ventilation. However, such strategies can be challenging in pediatric populations due to technical limitations, and also lead to ventilator induced lung injury. We report two unique cases that support the use of venovenous extracorporeal membrane oxygenation as an alternative strategy for management of unilateral lung disease in children.