The aim of this review is to highlight the chemopreventive properties of hydroxy-substituted natural and synthetic chalcones along with a number of their analogs. These products display various biological activities, and have many applications against various diseases. Antioxidant and anti-inflammatory properties of chalcones bearing hydroxy substituents are underlined. The influence of hydroxy substituents located on ring A, B, or both are systematized according to the exhibited biological properties.