Abiotic stress conditions such as drought, heat, or salinity cause extensive losses to agricultural production worldwide. Progress in generating transgenic crops with enhanced tolerance to abiotic stresses has nevertheless been slow. The complex field environment with its heterogenic conditions, abiotic stress combinations, and global climatic changes are but a few of the challenges facing modern agriculture. A combination of approaches will likely be needed to significantly improve the abiotic stress tolerance of crops in the field. These will include mechanistic understanding and subsequent utilization of stress response and stress acclimation networks, with careful attention to field growth conditions, extensive testing in the laboratory, greenhouse, and the field; the use of innovative approaches that take into consideration the genetic background and physiology of different crops; the use of enzymes and proteins from other organisms; and the integration of QTL mapping and other genetic and breeding tools.