Hibernators offers natural models of mammalian organ systems that can withstand long-term hypothermia and ischemia. The biochemical mechanisms that regulate and stabilize metabolism to assure long-term viability during torpor can be applied in methodologies that could improve the hypothermic preservation of human organs removed for transplant and substantially increase both the time that organs can be maintained in cold storage and the recovery of function after implantation. The present review assesses four current areas of hibernation research that have applied relevance for hypothermic preservation: (1) reversible phosphorylation control of metabolism, (2) preservation of cellular protein synthesis machinery during torpor, (3) hibernation-specific gene expression, and (4) extracellular signaling and preconditioning. Particular emphasis is placed on the application of new techniques in genomics - the use of cDNA array screening - for identifying gene responses that underlie both hypothermic injury in nonhibernators and protective responses by hibernating mammals.