The ability of organisms to withstand water stress is a fundamental determinant of their abundance and distribution. The ability to survive periods of water loss (“desiccation resistance”) is also related to the ability of species to become invasive pests. This is equally true of the true fruit flies (Diptera: Tephritidae), which include highly invasive, damaging pests of fruit and vegetable production. This chapter describes current knowledge of the desiccation resistance of tephritid species. Patterns of whole-organism desiccation resistance are summarized for the egg, larval, pupal, and adult life stages. Associations of desiccation resistance in tephritids with body size, body water content, and lipid content are explained. Artificial selection for desiccation resistance as a means to improve the performance of sterile 28males in sterile insect technique (SIT) programs is examined. With few exceptions, desiccation resistance of the adult and pupal stages of tephritid species is best studied. Adult desiccation resistance is much higher than anticipated. At least in Ceratitis capitata (Wiedemann), this may result from the ability to use water released by lipid catabolism. However, there is also considerable evidence of variation in adult desiccation resistance within species in relation to environmental variability, sex, age, and genetic background. As a consequence, there is capacity for adult tephritid desiccation resistance to be improved by artificial selection through water stress in the laboratory. It is necessary to improve taxonomic, life stage, and life history coverage of studies on tephritid desiccation resistance. Building on results available to date will improve our understanding of the genetic and physiological mechanisms conferring desiccation resistance and develop tephritid strains that can tolerate water stress. By doing so, a better understanding of responses by nonpest tephritids to a changing world and an improved management of pest tephritids will be achieved.