Advances in extracorporeal life support have expanded indications for use extending beyond patients undergoing cardiac surgery. The approach to cannulation in patients requiring extracorporeal membrane oxygenation should be individualized and based on the specific clinical scenario in which the need arises. Adherence to proper techniques of vessel visualization, exposure, and cannulation along with accurate placement of cannulae will optimize flows and minimize complications in this setting. Patients in need of mechanical circulatory support require input from a multidisciplinary team approach with systematic clinical evaluation to optimize outcome. If hemodynamics do not initially permit the successful separation from mechanical support, then a systematic search for potentially reversible patient and/ or pump related factors should be undertaken. The success of this therapy is predicated on patient selection, a multidisciplinary team approach in the intensive care unit, adherence to precise technical principles, and repeated patient evaluation.