The anatomical interaction between mechanical circulatory or respiratory support and the patient is achieved by specially designed tubes called cannulae. Despite advancements in cannula design for ventricular assist devices (VADs), extracorporeal membrane oxygenation (ECMO), and total artificial hearts (TAH), cannula-related complications such as bleeding and thrombus formation remain prevalent. There is no “gold standard” cannula design, with almost all clinically used devices incorporating a unique cannula design or placement. Inflow (flow from patient to device) and outflow (flow from device to patient) cannula design has focused on methods to deliver sufficient cardiac output, improve vessel flow dynamics, reduce postoperative bleeding, and other anatomical considerations. However, continued development of VAD, ECMO, and TAH cannula design is required to reduce postoperative complications and improve patient outcomes.