As global warming progresses, agriculture will likely be impacted enormously by the increasing heat stress (HS). Hence, future crops, especially in the southern Mediterranean regions, need thermotolerance to maintain global food security. In this regard, plant scientists are searching for solutions to tackle the yield-declining impacts of HS on crop plants. Glycine betaine (GB) has received considerable attention due to its multiple roles in imparting plant abiotic stress resistance, including

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... o high temperature. Several studies have reported GB as a key osmoprotectant in mediating several plant responses to HS, including growth, protein modifications, photosynthesis, gene expression, and oxidative defense. GB accumulation in plants under HS differs; therefore, engineering genes for GB accumulation in non-accumulating plants is a key strategy for improving HS tolerance. Exogenous application of GB has shown promise for managing HS in plants, suggesting its involvement in protecting plant cells. Even though overexpressing GB in transgenics or exogenously applying it to plants induces tolerance to HS, this phenomenon needs to be unraveled under natural field conditions to design breeding programs and generate highly thermotolerant crops. This review summarizes the current knowledge on GB involvement in plant thermotolerance and discusses knowledge gaps and future research directions for enhancing thermotolerance in economically important crop plants.