When plants colonized land they developed a wide range of adaptations to cope with life in a drier environment. One key adaptation was desiccation tolerance (DT) which is the ability to survive the removal of almost all cellular water without irreparable damage. DT is recurrent in orthodox seeds and in the vegetative body of species commonly known as ‘resurrection plants’. In this thesis a multilevel approach, combining genomics, transcriptomics, gene family evolution, protein structural and functional analysis, and seed physiology was employed in order to tackle curiosity-driven fundamental questions about the major mechanisms governing DT. Several mechanisms were found to be important for DT, including the coordinated activation of cell protection through Late Embryogenesis Abundant (LEA) proteins, which were shown to be common amongst resurrection plants and orthodox seeds. These findings aid to the comprehension of the complexity of DT in plants, and may provide transferrable knowledge to design more water-stress tolerant crops.