Desiccation-tolerance, the ability to revive from the air-dried state, is found in prokaryotes, algae and bryophytes, and occasionally in pteridophytes, but is very rare in the vegetative tissues of angiosperms or in animal tissues. However, the vast majority of lichens are desiccation-tolerant. Under natural conditions, the life of most lichens is characterized by rapidly changing water contents, and correspondingly rapidly changing physiological activity such as respiration and photosynthesis. Taken to the extreme, some lichens can revive after being desiccated under controlled laboratory conditions for many months. As a result of their desiccation-tolerance, lichens are extremophiles and can live in places no higher plant can. They may be the predominant life-form in ecosystems characterized by severe environmental stresses such as Arctic, Antarctic and alpine regions, as well as deserts. This review critically assesses our current knowledge about desiccation-tolerance in lichens, concentrating on mechanisms that protect from desiccation-induced damage. Evidence available from other desiccation-tolerant life-forms suggests that desiccation-tolerance is a multifaceted trait involving a suite of interacting mechanisms. The majority of recent studies on mechanisms of lichen desiccation-tolerance have focused on the scavenging of reactive oxygen species, which therefore forms a major part of this review. It is argued that effective control of reactive oxygen species and mutual up-regulation of protective mechanisms was critically important for the evolution of lichens, facilitating the transition from free-living fungi and green algae or cyanobacteria to the lichenized state. Recently developed tools of molecular biology, particularly from the -omics disciplines, have only just started to be applied to lichens. There remain many unsolved questions as to how lichens survive desiccation and the authors hope to encourage more scientists to investigate this intriguing phenomenon.