When confronted with severe environmental stress, some animals are able to undergo a substantial reorganization of their cellular environment that enables long-term survival. One molecular mechanism of adaptation that has received considerable attention in recent years has been the action of reversible transcriptome regulation by microRNA. The implementation of new computational and high-throughput experimental approaches has started to uncover the vital contributions of microRNA towards stress adaptation. Indeed, recent studies have suggested that microRNA may have a major regulatory influence over a number of cellular processes that are essential to prolonged environmental stress survival. To date, a number of studies have highlighted the role of microRNA in the regulation of a metabolically depressed state, documenting stress-responsive microRNA expression during mammalian hibernation, frog and insect freeze tolerance, and turtle and marine snail anoxia tolerance. These studies collectively indicate a conserved principle of microRNA stress response across phylogeny. As we are on the verge of dissecting the role of microRNA in environmental stress adaptation, this review summarizes recent research advances and the hallmark expression patterns that facilitate stress survival.