Desiccation tolerance appeared as the key adaptation feature of photoautotrophic organisms for survival in terrestrial habitats. During the further evolution, vascular plants developed complex anatomy structures and molecular mechanisms to maintain the hydrated state of cell environment, which essentially increased their ability to sustain water deficit and dehydration. However, the role of the genes encoding the mechanisms behind this adaptive feature in the higher vascular plants is restricted to the dehydration protection of spores, seeds and pollen, whereas the mature vegetative stages became sensitive to desiccation. During maturation, orthodox seeds lose up to 95% of their water and successfully enter dormancy. This feature allows seeds maintaining their viability even under strongly fluctuating environmental conditions. The mechanisms behind the desiccation tolerance are activated at the late seed maturation stage and are associated with the accumulation of late embryogenesis abundant proteins (LEA proteins), small heat shock proteins (sHSP), non-reducing oligosaccharides, and antioxidants of different chemical nature. The main regulators of maturation and desiccation tolerance onset are abscisic acid and protein DOG1, which control the network of transcription factors, among which are LEC1, LEC2, FUS3, ABI3, ABI5, AGL67, PLATZ1, PLATZ2. This network is complemented by epigenetic regulation of gene expression by methylation of DNA, post-translational modifications of histones and chromatin remodeling impact on seed desiccation tolerance and longevity. Moreover, orthodox seeds are able to maintain desiccation tolerance during germination up to the stage of radicle protrusion. This time point is critical in the process of seed development, as the seeds lose desiccation tolerance at this moment.