Drying to equilibrium with the air is lethal to most species of animals and plants, making drought (i.e., low external water potential) a central problem for terrestrial life and a major cause of agronomic failure and human famine. Surprisingly, a wide taxonomic variety of animals, microbes, and plants do tolerate complete desiccation, defined as water content below 0.1 g H₂O g⁻¹ dry mass. Species in five phyla of animals and four divisions of plants contain desiccation-tolerant adults, juveniles, seeds, or spores. There seem to be few inherent limits on desiccation tolerance, since tolerant organisms can survive extremely intense and prolonged desiccation. There seems to be little phylogenetic limitation of tolerance in plants but may be more in animals. Physical constraints may restrict tolerance of animals without rigid skeletons and to plants shorter than 3 m. Physiological constraints on tolerance in plants may include control by hormones with multiple effects that could link tolerance to slow growth. Tolerance tends to be lower in organisms from wetter habitats, and there may be selection against tolerance when water availability is high. Our current knowledge of limits to tolerance suggests that they pose few obstacles to engineering tolerance in prokaryotes and in isolated cells and tissues, and there has already been much success on this scientific frontier of desiccation tolerance. However, physical and physiological constraints and perhaps other limits may explain the lack of success in extending tolerance to whole, desiccation-sensitive, multicellular animals and plants. Deeper understanding of the limits to desiccation tolerance in living things may be needed to cross this next frontier.