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Esca is an increasing threat to global viticulture causing significant losses by reducing yields, declining or wilting vines, and shortening the productive life of vineyards. Recent findings indicate that the disease may also affect the quality of grapes and the chemical composition of musts and wines. However, more research in this field is needed. Esca seems to affect the ripening process of grapes resulting in lower sugar content, higher acidity, and increased nitrogen concentrations. Regarding polyphenolic compounds, reduction on the concentrations of (+)-catechin, (−)-epicatechin, anthocyanins, and tannins has been observed due to the alteration of flavonoid metabolism. Esca is a complex-chronic disease, where several fungal pathogens act simultaneously or successively, to cause necrosis to the vascular tissues of grapevines by blocking the xylem vessels and by producing enzymes and phytotoxic metabolites. As genotype affects stress response, specific Vitis vinifera cultivars present higher levels of resistance to the disease than others. There is evidence that varieties such as Merlot, Grenache Rouge, and Roussanne are relatively resistant, compared with more susceptible Cabernet Sauvignon, Mourvèdre, Sauvignon Blanc, and Semillon. Another main objective of the current work was to investigate the possible effects of climate change on Esca development and propose appropriate control strategies.