Hibernators are unique among mammals in their ability to attain, withstand, and reverse low body temperatures. Hibernators repeatedly cycle between body temperatures near zero during torpor and 37 degrees C during euthermy. How do these mammals maintain cardiac function, cell integrity, blood fluidity, and energetic balance during their prolonged periods at low body temperature and avoid damage when they rewarm? Hibernation is often considered an example of a unique adaptation for low-temperature function in mammals. Although such adaptation is apparent at the level of whole animal physiology, it is surprisingly difficult to demonstrate clear examples of adaptations at the cellular and biochemical levels that improve function in the cold and are unique to hibernators. Instead of adaptation for improved function in the cold, the key molecular adaptations of hibernation may be to exploit the cold to depress most aspects of biochemical function and then rewarm without damage to restore optimal function of all systems. These capabilities are likely due to novel regulation of biochemical pathways shared by all mammals, including humans.