The phytochemicals present in fruits and vegetables may play an important role in deceasing chronic disease risk. Grapes, one of the most popular and widely cultivated and consumed fruits in the world, are rich in phytochemicals. Epidemiological evidence has linked the consumption of grapes with reduced risk of chronic diseases, including certain types of cancer and cardiovascular disease. In vitro and in vivo studies have shown that grapes have strong antioxidant activity, inhibiting cancer cell proliferation and suppressing platelet aggregation, while also lowering cholesterol. Grapes contain a variety of phytochemicals, like phenolic acids, stilbenes, anthocyanins, and proanthocyanidins, all of which are strong antioxidants. The phytochemical composition of grapes, however, varies greatly among different varieties. While extensive research exists, a literature review of the health benefits of grapes and their phytochemicals has not been compiled to summarize this work. The aim of this paper is to critically review the most recent literature regarding the concentrations, biological activities, and mechanisms of grape phytochemicals.