The contribution of vine cultivation to human welfare as well as the stimulation of basic social and cultural features of civilization has been great. The wide temporal and regional distribution created a wide array of genetic variants that have been used as propagating material to promote cultivation. Information on the origin and relationships among cultivars is of great interest from a phylogenetics and biotechnology perspective. Fingerprinting and exploration of the complicated genetic background of varieties may contribute to future breeding programs. In this review, we present the most frequently used molecular markers, which have been used on Vitis germplasm. We discuss the scientific progress that led to the new strategies being implemented utilizing state-of-the-art next generation sequencing technologies. Additionally, we attempted to delimit the discussion on the algorithms used in phylogenetic analyses and differentiation of grape varieties. Lastly, the contribution of epigenetics is highlighted to tackle future roadmaps for breeding and exploitation of Vitis germplasm. The latter will remain in the top of the edge for future breeding and cultivation and the molecular tools presented herein, will serve as a reference point in the challenging years to come.