Polyphenols have been demonstrated to have clear antioxidant activities in vitro. However, in complex biological systems, they exhibit additional properties which are yet poorly understood. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathologic processes, leading to proliferative or degenerative diseases. Polyphenols can directly interact with specific steps and/or proteins regulating the apoptotic process in different ways depending on their concentration, the cell system, the type or stage of the pathological process. A growing body of in vitro evidence has provided interesting insights in the comprehension of the cellular and molecular mechanisms responsible for the modulation of apoptosis. However additional and harder studies are needed to better elucidate the mechanisms of action and the real in vivo effectiveness of polyphenols in order to propose them as potential candidates for chemoprevention and treatment of cancer and cardiovascular diseases.