The inverse association between alcohol intake and coronary heart disease has been consistently reported in cross-culture, case-control, and cohort studies. Over the past couple of decades, however, many studies have explained promising health benefits associated with wine consumption. Some studies suggest that red wine is more cardioprotective than white wine, possibly due to the increased content of flavanoid antioxidants found in red wine. Several experimental studies, including ours, support the evidence that these beneficial effects are due to resveratrol, the polyphenolic compound present in red wine. Many studies have provided evidence that resveratrol possesses antioxidant and antiapoptotic effects apart from activation of longevity proteins (such as SIRT-1). We have recently reported the angiogenic, antihypercholesterolemic, and antidiabetic effects of resveratrol and the mechanisms involved in reduced ventricular remodeling and increased cardiac functions. We have also shown different strategic target molecules involved in resveratrol-mediated cardioprotection. Therefore, this review discusses the potential effect of resveratrol and the mechanisms involved in resveratrol-mediated cardioprotection during myocardial infarction, hypercholesterolemia, and diabetes rendering its beneficial effects during health and disease.