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• The co-occurrence of heat and water-deficit stress during flowering negatively impacts crop productivity. • Heat, water-deficit, and their combination alter developmental processes associated with plant reproduction. • Stress-induced changes in sugar metabolism, reactive oxygen species and hormone levels are thought to play a role in yield reduction during stress combination. • Understanding the molecular processes associated with yield reduction during stress combination would allow the development of climate-resilient crops. Historically, extended droughts combined with heat waves caused severe reductions in crop yields estimated at billions of dollars annually. Because global warming and climate change are driving an increase in the frequency and intensity of combined water-deficit and heat stress episodes, understanding how these episodes impact yield is critical for our efforts to develop climate change-resilient crops. Recent studies demonstrated that a combination of water-deficit and heat stress exacerbates the impacts of water-deficit or heat stress on reproductive processes of different cereals and legumes, directly impacting grain production. These studies identified several different mechanisms potentially underlying the effects of stress combination on anthers, pollen, and stigma development and function, as well as fertilization. Here we review some of these findings focusing on unbalanced reactive oxygen accumulation, altered sugar concentrations, and conflicting functions of different hormones, as contributing to the reduction in yield during a combination of water-deficit and heat stress. Future studies focused on the effects of water-deficit and heat stress combination on reproduction of different crops are likely to unravel additional mechanisms, as well as reveal novel ways to develop stress combination-resilient crops. These could mitigate some of the potentially devastating impacts of this stress combination on agriculture. [ABSTRACT FROM AUTHOR]