Simple SummaryGlobal warming has caused a significant extension of the duration and the mean temperatures of summers; this is a serious stressor for dairy cows that are particularly sensitive to the high temperatures. Under these conditions, the productivity and the fertility of the animals are seriously compromised leading to considerable financial losses to the farmers. A deep understanding of the prevailing mechanisms of the cow to withstand this serious stressor, is prerequisite for planning and implementation of heat stress mitigation programs. To this end, in this review we analyze the main hormonal and molecular alterations that take place during heat stress, and which directly or indirectly affect cow’s fertility.AbstractGlobal warming is a significant threat to the sustainability and profitability of the dairy sector, not only in tropical or subtropical regions but also in temperate zones where extreme summer temperatures have become a new and challenging reality. Prolonged exposure of dairy cows to high temperatures compromises animal welfare, increases morbidity, and suppresses fertility, resulting in devastating economic losses for farmers. To counteract the deleterious effects of heat stress, cattl e employ various adaptive thermoregulatory mechanisms including molecular, endocrine, physiological, and behavioral responses. These adaptations involve the immediate secretion of heat shock proteins and cortisol, followed by a complex network of disrupted secretion of metabolic and reproductive hormones such as prolactin, ghrelin, ovarian steroid, and pituitary gonadotrophins. While the strategic heat stress mitigation measures can restore milk production through modifications of the microclimate and nutritional interventions, the summer fertility records remain at low levels compared to those of the thermoneutral periods of the year. This is because sustainment of high fertility is a multifaceted process that requires appropriate energy balance, undisrupted mode of various hormones secretion to sustain the maturation and fertilizing competence of the oocyte, the normal development of the early embryo and unhampered maternal—embryo crosstalk. In this review, we summarize the major molecular and endocrine responses to elevated temperatures in dairy cows, as well as the impacts on maturing oocytes and early embryos, and discuss the consequences that heat stress brings about in dairy cattle fertility.