© 2013 Springer Science+Business Media New York. All rights reserved. Two types of changes have been documented in the brain-dead potential organ donor. The first is due to diffuse vascular and interstitial injury and the second results from diffuse metabolic cellular disturbances. The former is secondary to the autonomic storm that takes place from excessive sympathetic activity during the development of brain death. The latter is due to endocrine abnormalities following loss of hypothalamic control, leading to a state of progressive inhibition of aerobic metabolism. Several clinical studies failed to document low levels of free T3, T4, cortisol, and/or insulin after brain death and/or failed to demonstrate any significant beneficial cardiac and circulatory effect of T3/T4 administration. However, the effects of hormonal therapy were tested by other groups in the management of the brain-dead potential organ donor and demonstrated a beneficial clinical effect in the hemodynamically unstable donor. Data compiled by the United Network of Organ Sharing (UNOS) from a large number of transplant centers have provided supportive evidence for the beneficial effects of hormonal therapy on donor organ function both before and after the transplant procedure. In 2009, almost 50% of brain-dead potential donors in the USA received some form of hormonal replacement therapy.