Numerous studies indicate that damage of the genetic material plays a crucial role in a variety of human diseases, in particular in the etiology of cancer. Human, animal and also in vitro studies provide evidence that coffee and specific constituents (e.g. chlorogenic acids, N-methylpyridinium, caffeine and diterpenoids) prevent DNA damage. Among the most relevant molecular mechanisms which have been identified so far are prevention of inflammations and of oxidative damage of the genetic material as well as protection against genotoxic carcinogens found in human foods (heterocyclic aromatic amines, polycyclic aromatic hydrocarbons and mycotoxins). These effects are caused by induction of antioxidant and drug detoxifying (phase II) enzymes. It is possible that cancer protective properties of coffee (e.g. prevention of hepatocellular carcinoma) as well as other beneficial health effects (improvement of male fertility and prevention of neurodegenerative disorders) are due to the antimutagenic properties of coffee, but further investigations are required to elucidate these associations.