Heart transplantation is a widely accepted therapy for the treatment of end-stage cardiac disease. Approximately 20,000 people in the United States now live with a transplanted heart. Survival is nearly 90% at 1 year, 74.0% at 5 years, and the median survival is more than 10 years. Although long-term outcomes of cardiac transplantations have steadily improved, numerous life-threatening complications persist, including infection, allograft rejection, and allograft vascular disease. Allograft rejection is most frequent within the first month following transplantation and declines progressively thereafter. Endomyocardial biopsy is currently the standard for detecting allograft rejection after heart transplantation. Typically, the patient will have biopsies to monitor for rejection weekly for the first 4 to 6 weeks after transplantation, biweekly until the third month, monthly to 6 months, and then every 1 to 3 months as indicated. However, as endomyocardial biopsies are invasive and have several limitations, alternative noninvasive techniques to detect and monitor allograft rejection, including molecular expression testing, are under investigation.