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Drought is undoubtedly a major environmental constraint that negatively affects agricultural yield and productivity throughout the globe. Plants are extremely vulnerable to drought which imposes several physiological, biochemical and molecular perturbations. Increased generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in different plant organs is one of the inevitable consequences of drought. ROS and RNS are toxic byproducts of metabolic reactions and poise oxidative stress and nitrosative stress that are detrimental for plants. In spite of toxic effects, these potentially active radicals also play a beneficial role in mediating several signal transduction events that lead to plant acclimation and enhanced survival under harsh environmental conditions. The precise understanding of ROS and RNS signaling and their molecular paradigm with different phytohormones, such as auxin, gibberellin, cytokinin, abscisic acid, ethylene, brassinosteroids, strigolactones, jasmonic acid, salicylic acid and melatonin play a pivotal role for maintaining plant fitness and resilience to counteract drought toxicity. Therefore, the present review provides an overview of integrated systemic signaling between ROS, RNS and phytohormones during drought stress based on past and recent advancements and their influential role in conferring protection against drought-induced damages in different plant species. Indeed, it would not be presumptuous to hope that the detailed knowledge provided in this review will be helpful for designing drought-tolerant crop cultivars in the forthcoming times. [Display omitted] • Drought can cause serious threat to agricultural crop production, thereby affecting global food security. • Excess generation of ROS and RNS during drought act as a signal for phytohormone accumulation for ROS and RNS scavenging. • Crosstalk between ROS, RNS and phytohormone signaling plays pivotal role in understanding drought stress tolerance mechanism. • Drought-induced overproduction of ROS and RNS regulates stomatal closure. [ABSTRACT FROM AUTHOR]