The INTERMACS registry has played a central role in the evolving field of device therapy for advanced heart failure (HF). This nationwide, prospective registry of approved assist devices has defined the boundaries of mechanical support, tracked the evolution from pulsatile to continuous flow, developed new profiles for advanced HF, and standardized adverse event definitions. INTERMACS has guided current therapy and in the future will do so aided by new insights from MedaMACS, a parallel registry of medically-managed ambulatory patients with advanced HF. Together INTERMACS and MedaMACS will leverage the power of observation research to guide patient-centered decisions about mechanical circulatory support.