Vegetative desiccation tolerance occurs in a unique group of species termed 'resurrection plants'. Here, we review the molecular genetic, physiological, biochemical, ultrastructural and biophysical studies that have been performed on a variety of resurrection plants to discover the mechanisms responsible for their tolerance. Desiccation tolerance in resurrection plants involves a combination of molecular genetic mechanisms, metabolic and antioxidant systems as well as macromolecular and structural stabilizing processes. We propose that a systems-biology approach coupled with multivariate data analysis is best suited to unraveling the mechanisms responsible for plant desiccation tolerance, as well as their integration with one another. This is of particular relevance to molecular biological engineering strategies for improving plant drought tolerance in important crop species, such as maize (Zea mays) and grapevine (Vitis vinifera).