The production of oxidative species (free radicals) is very common in many types of cancer cells. This oxidative stress has been associated with the carcinogenic process as it can damage cellular proteins and lipids and form DNA adducts. Antioxidants interact with these oxidative species and reduce their (pro)neoplastic activity. Therefore, intake of antioxidants has been hypothesized to interfere with carcinogenesis. Chemoprevention by dietary or supplemental antioxidants is a strategy which aims at reducing the incidence and prevalence of cancer. Antioxidants are present in plant food and considerable knowledge has been obtained on the mechanisms by which these phytochemicals interact with the carcinogenic process. In general, antioxidants prevent oxidative species to reach a sufficient intracellular level to promote carcinogenesis. However, oxidative species do not only have a detrimental effect. At physiological levels they also confer prevention by inducing immunoresponses and apoptosis in order to remove the damaged cells. These beneficial actions are of extreme value for normal organ function, and it casts doubt on the use of supplemental antioxidants. Indeed, from recent high-quality epidemiological studies the image emerges that supplemental antioxidants may help to prevent cancer only in diet-deficient populations or individuals. This paper aims at providing an overview on the knowledge about the most common (dietary) antineoplastic chemoprevention agents and the clinical results obtained from epidemiological studies in this field.