The pathophysiology of true frostbite reveals that the direct injury produced during the initial freeze process has a minor contribution to the global tissue damage. However, rapid rewarming to reverse the tissue crystallization has essentially been the lone frostbite intervention for almost half a century. The major pathologic process is the progressive microvascular thrombosis following reperfusion of the ischemic limb, with the cold-damaged endothelial cells playing a central role in the outcome of these frozen tissues. Newer interventions offer the opportunity to combat this process, and this article offers a scientific approach to frostbite injuries of the upper extremities.