Heat stress (HS) is a serious environmental stress that negatively affects crop growth and productivity across the globe. The recent increase in atmospheric temperature caused by global warming has increased its intensity, which is a serious challenge that needs to be addressed. Plant growth and development involves a series of physiological, metabolic, and biochemical processes that are negatively affected by heat-induced oxidative stress, disorganization of cellular membranes and disturbed plant water relations, nutrient uptake, photosynthetic efficiency, and antioxidant activities. Plant tolerance to abiotic stresses can be substantially increased by the application of bio-stimulants, without posing a threat to the ecosystem. Melatonin (MT) is a multi-functional signaling molecule that has the potential to protect plants from the adverse impacts of HS. MT protects the cellular membranes, maintains the leaf water content, and improves the water use efficiency (WUE) and nutrient homeostasis; thereby, improving plant growth and development under HS. Moreover, MT also improves gene expression, crosstalk of hormones, and osmolytes, and reduces the accumulation of reactive oxygen species (ROS) by triggering the antioxidant defense system, which provides better resistance to HS. High endogenous MT increases genes expression and antioxidant activities to confer HS tolerance. Thus, it is important to understand the detailed mechanisms of both exogenous and endogenous MT, to induce HS tolerance in plants. This review highlights the versatile functions of MT in various plant responses, to improve HS tolerance. Moreover, we also discussed the MT crosstalk with other hormones, antioxidant potential of MT, and success stories of engineering MT to improve HS tolerance in plants. Additionally, we also identified various research gaps that need to be filled in future research using this important signaling molecule. Thus, this review will help the readers to learn more about MT under changing climatic conditions and will provide knowledge to develop heat tolerance in crops. View Full-Text