With more than 8000 polyphenols found in food (mainly, wine, tea, coffee, cocoa, vegetables and cereals), many epidemiological studies suggest that the intake of polyphenol-rich foods has a beneficial effect on a large number of cardiovascular risk factors, such as high blood pressure, high blood cholesterol, obesity, diabetes and smoking. The mechanisms involved in the cardioprotective effects of polyphenols are numerous and include antioxidant, vasodilator, anti-inflammatory, anti-fibrotic, antiapoptotic and metabolic. Most importantly, recent experimental data demonstrate that polyphenols can exert its cardioprotective effect via the activation of several powerful prosurvival cellular pathways that involve metabolic intermediates, microRNAs, sirtuins and mediators of the recently described reperfusion injury salvage kinases (RISK) and survivor activating factor enhancement (SAFE) pathways.