Early studies focused on the negative effects on color and flavor of foods, followed by exploration of the antioxidant properties and the associated health benefits. The growing body of evidence suggests that plant-based polyphenols may help prevent or delay the onset of a multiplicity of diseases. Newer work suggests that a variety of polyphenols can alter the expression of genes in the inflammatory pathway. Data also show that the absorption of the polyphenols is very limited. Insulin resistance and endothelial and mitochondrial dysfunction are hallmarks of the metabolic syndrome and aging and occur at the early stages of the disease. There is limited clinical evidence that certain polyphenolic metabolites by virtue of their anti-inflammatory activities can improve insulin sensitivity and endothelial and mitochondrial function, suggesting that polyphenols are good for disease prevention. The goal of this review is to summarize the evolution and emphasize the potential benefits of polyphenols.