Breeding programs for disease resistance were developed from the 19th century on, in both the old (Europe) and new world as a way to promote sustainable viticulture. The main results of breeding, in terms of disease resistance and grape (and wine) quality are described, ranging from the first American hybrids to the most recent varieties. The activity of some representative breeders is discussed and the current situation in Italy is reported. Productive, legislative, and commercial aspects for wine production are considered, especially for European Union where the wine sector is strongly regulated. The perspectives of breeding for disease resistance are discussed, including the new breeding techniques (Nbt) like cis-genesis and genome editing. The importance to interact with the society to make acceptable these innovations is emphasized. While less acceptance problems are expected with table grapes, raisins or rootstocks, more concerns might arise with wine grapes. The role of science is to give the legislator tools to cope with sustainability and to educate the society (from the grape grower to the wine consumer) to a correct understanding. Innovations can be a real advantage only if they are accepted by all the actors of the wine chain.