The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavanols and resveratrol are the most important grape polyphenols because they possess many biological activities such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. Grape-related anti-tumoral activity encompasses a wide array of biological mechanisms and cellular targets, eventually leading to inhibition of cell growth and to enhanced apoptosis in several cancer cell lines, including lung, colon, breast, bladder, leukemia and prostate tumors. Those effects are likely modulated at the molecular level through selectively modulating the redox balance and displaying anti-oxidant as well as pro-oxidant actions. GSE-related anti-cancer activity mostly relies on the induced increase in reactive oxygen species, followed by the orchestrated down- and up-regulation of several key-molecular pathways, including MAPK kinases, PI3K/Akt, NF-kB, cytoskeleton proteins and metalloproteinases. Promising results obtained in vitro as well as on animal studies suggest that GSE may have a great relevance as source of potential new pharmacological molecules,and could represent an important opportunity for clinical research.