Modern viticulture in Croatia and the world is based mainly on varieties that are sensitive to various diseases and pests, which results in the unsustainably large amounts of pesticides used in grape production. The sustainable development of viticulture in the future will only be possible by increasing the resistance of the grapevine through the development of new varieties resistant to diseases and abiotic stresses caused by climate change. Breeding programs have been launched in the leading wine-growing countries to develop new varieties with resistance to diseases (resistant varieties), which at the same time show a high level of quality. New resistant varieties were most often created based on international varieties (mainly French and German) using classical breeding and selection supported by genetic markers (MAS - Marker Assisted selection). Croatia is rich in autochthonous grape varieties that are the basis of wine production, and are not present in the breeding programs of other countries. In 2015, the applicant started a breeding program whose long-term goal is the development of resistant varieties of grapevines with stable and durable resistance, using autochthonous germplasm in combination with different sources of resistance that are present in the resistant varieties developed so far suitable for growing in Croatia. This project has a goal to improve the process of grapevine breeding through the development of the application of metabolomic biomarkers associated with disease resistance or reduced sensitivity to water stress and high temperatures, high-throughput phenotyping, the application of existing selection methods based on molecular markers with the aim of pyramiding resistance, and the development of the method for early assessment of grape quality in the selection process. This way breeding process can be improved concerning speed and efficiency for the development of cultivars with permanent and stable resistance to diseases.