Abstract: Impact of water stress on growth and yield of wheat (Triticum aestivum vulgare L.) with and without foliar spraying 5-amino Levulinic Acid (5-ALA) was studied. Role of 5-ALA on water use efficiency under water stress was also evaluated. Results showed that irrigation wheat weekly was associated with the highest biological and grain yields ha-1. Water stress by prolonging irrigation interval to 21 days resulted in a significant reduction in all estimated characters, except harvest index. However, maximum Water Use Efficiency of Biological Yield (WUEB) produced with the irrigation every 14 days. 5-ALA enhanced growth and increased yield of wheat, compared with the control. Foliar spraying of 100 ppm 5-ALA ha-1 produced the highest biological and grain yields ha-1 as well as water use efficiency. Application of 100 ppm 5-ALA enhanced the tolerance of wheat to water stress. The interaction between irrigation treatments and 5-ALA concentrations significantly affected biological and grain yields ha-1 as well as WUEB and WUEG (Water Use Efficiency of Grain yield). Wheat plants that irrigated every 14 days and foliar sprayed with 50-100 ppm 5-ALA ha-1 out yielded and surpassed in WUE that grown under normal water status (irrigation every 7) and left without 5-ALA application. So, it can be concluded that foliar application of 5-AlA on wheat plants grown under drought condition as in Saudi Arabia can enhance the tolerance to drought and increase grain yield.