Until the middle of the last decade, few people had heard of microRNAs (miRNAs), 21- to 23-nucleotide conserved RNAs. MicroRNAs represent a new paradigm because they regulate most physiological processes and thus have immense potential for medical advancement. Resveratrol, a red wine-derived polyphenolic compound, has been shown to have significant effects in various disease models, such as cardioprotection in ischemic heart, diabetes, and chemoprevention of cancers. The targets of resveratrol include various pathways and molecules, such as sirtuins, FOXOs, and autophagy. The successful application of resveratrol lies in understanding its mechanisms of action through direct and indirect interactions with pathways, including miRNAs. For example, a unique miRNA footprint is present in the heart treated with resveratrol. Targets of those miRNAs have potential implications for physiological and pathophysiological processes in health and disease.