The current strategy to control grapevine downy and powdery mildew relies on chemical treatments. An alternative solution to the use of chemicals is the development of varieties resistant to pathogens. Several genetic factors derived from Vitis species closely related to cultivated grapevine and conferring protection against downy mildew or powdery mildew have already been identified. Nevertheless, many major resistance genes have been overcome by virulent strains of pathogens in various plant-pathogen interactions, and such resistance breakdowns have already been described in grapevine. Resistance genes are a limited resource, and their introduction in a new variety is a long-term and costly process. This is why the assessment and improvement of resistance durability is crucial, particularly in the case of a perennial species. The Inra-ResDur breeding program aims at creating varieties with durable resistance to downy and powdery mildew. The pyramiding strategy employed to limit the risk of resistance breakdown is described. Other innovative ways are proposed to enhance resistance durability.