Over the past 30 years, heart transplantation has evolved into a definitive therapy for patients with end-stage cardiomyopathy. However, perioperative management of patients undergoing heart transplantation remains a challenge for anesthesiologists. The presence of biventricular failure, arrhythmias and associated multisystem organ dysfunction may contribute to significant intraoperative hemodynamic instability prior to the initiation of cardiopulmonary bypass (CPB). Even after an uneventful transplantation, weaning from CPB may be difficult. Acute right ventricular failure can develop in the recipient secondary to pre-existing pulmonary hypertension. Treatment options frequently focus on therapeutic interventions directed towards decreasing pulmonary vascular resistance and improving right ventricular contractility. Intraoperative use of transesophageal echocardiography (TEE) enables the anesthesiologist to diagnose acute right ventricular failure early on and guide therapy. Concurrent pathology including kinking of the pulmonary artery anastomosis or valvular insufficiency in the transplanted heart can also be recognized and addressed. The number of patients undergoing cardiac transplantation is continually increasing. In addition, the use of more effective immunosuppressive agents has curtailed transplant rejection and permitted longer survival. Consequently, heart transplant recipients are more frequently presenting for non-cardiac surgical procedures. Thus, an understanding of physiological and pharmacological implications associated with heart transplantation is crucial for managing these patients in the perioperative period.