Once considered risky and experimental, heart transplantation is now considered the treatment of choice for many people with severe heart failure. More than 2,000 heart transplants are performed annually in the United States. But because there are far more patients who need transplants than available donor hearts, the waiting lists for heart transplant are quite long. The principal challenge in heart transplantation is preventing the body’s immune system from attacking the donor heart (rejection), which requires administration of powerful immune suppressive drugs such as cyclosporine or tacrolimus. These drugs effectively suppress rejection if taken on a regular basis, but also increase the risk of certain infections and some cancers. With careful surveillance in specialized centers, heart transplant patients are now living longer than ever before, with average survival in the range of 10 to 15 years, and many surviving well beyond this.