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Abiotic stressors threaten the survival mechanism of plant life on Earth. Phytohormones are one of the defensive molecules produced by plants to counteract destructive effects elicited by abiotic stresses. In recent years, melatonin has gained prime importance in plant research because of its regulatory role in abiotic stress tolerance. Melatonin plays a central role in interacting with other phytohormones such as auxin, gibberellin, cytokinin, abscisic acid, ethylene, brassinosteroids, jasmonic acid, salicylic acid and plant growth regulators like nitric oxide, polyamines, γ-aminobutyric acid and serotonin to regulate stress alleviation for maintaining basal growth under harsh environmental conditions. The precise understanding of intricate web of crosstalk mechanisms among different phytohormones and their interconnected networks in terms of synergistic and antagonistic actions is crucial for maintaining cellular dynamics under unfavorable conditions. Therefore, in the present review, we mainly focused on crosstalk regulatory circuits operated by melatonin with other phytohormones at both physiological and molecular levels and their responses under known abiotic stress environment. The biosynthesis, signaling pathway and efficacy of melatonin in various stress avoidance are also enumerated in this review. Indeed, it would not be presumptuous to hope that this review will be helpful for designing climate-smart crop cultivars in the forthcoming years using melatonin as the major stress mitigator and endogenous signaling molecule during stressful situations. [Display omitted] • Biosynthesis of melatonin in plants is more complex than in animals. • Melatonin receptor CAND2/PMTR1 participates in melatonin-mediated signal perception, involving mitogen activated protein kinase-signaling cascades to enhance stress tolerance. • Melatonin interacts with different phytohormones for conferring stress protection. • Melatonin and phytohormones crosstalk operates synergistically or antagonistically, depending on the nature and complexity of stress, plant type and surrounding environment. [ABSTRACT FROM AUTHOR]