Use of extracorporeal membrane oxygenation (ECMO) in adults has surged in recent years. Typical configurations are venovenous (VV), which provides respiratory support, or venoarterial (VA), which provides both respiratory and circulatory support. In patients supported with VV ECMO who develop hemodynamic compromise, an arterial limb can be added (venovenous-arterial ECMO) to provide additional circulatory support. For patients on VA ECMO who develop concomitant respiratory failure in the setting of some residual cardiac function, an oxygenated reinfusion limb can be added to the internal jugular vein (venoarterial-venous ECMO) to improve oxygen delivery to the cerebral and coronary circulation. Such hybrid configurations can provide differential support for various forms of cardiopulmonary failure. We describe 21 patients who ultimately received a hybrid configuration at our institution between 2012 and 2013. Eight patients (38.1%) died during ECMO support, four patients (19.0%) died after decannulation but before hospital discharge, and nine patients (42.9%) survived to hospital discharge. Our modest survival rate is likely related to the complexity and severity of illness of these patients, and this relative success suggests that hybrid configurations can be effective. It serves patients well to maintain a flexible and adaptable approach to ECMO configurations for their variable cardiopulmonary needs.