Polyphenols are bioactive natural molecules biogenerated through secondary metabolic pathways. They are involved in different functions in the ecology, physiology, and biochemistry of plants such as chemical defense against predators and in plant-plant interferences. These compounds are known to have important biological activities related to human health such as antioxidant action, antiinflammatory and antimicrobial effects. The immense health benefits as well as use of many polyphenolic compounds as anti-infective agents against human pathogens have heightened the need for continuous supply of rare and expensive secondary metabolites. It has been demonstrated that the chemical structure of dietary polyphenols, such as the number and position of hydroxyl groups, can change their biological properties and bioavailability. This review focuses on prospects for, and success in metabolic engineering, including manipulation of structural regulatory genes to develop plants with tailor-made, optimized levels and composition of polyphenols.