For more than a century, medical investigators have sought to incriminate microorganisms in the cause of cancer. The first scientific evidence of such a relationship came in 1911, with the first successful induction of a tumor using a cell-free extract. Since that time, considerable data have accrued linking retroviruses, herpes viruses, the hepatitis B virus, papovaviruses, and adenoviruses to various malignant neoplasms. There is also increasing evidence that certain bacteria and parasites participate as cofactors in the development of some cancers. Although proof of cause-and-effect relationships has been difficult to obtain, there can be little doubt that microorganisms occasionally play pivotal roles in the origin of some cancers. Whether attempted intervention against these cancers is best directed against the oncogenic microorganisms themselves or against other environmental cofactors is not yet clear. Nevertheless, the successful application of tumor vaccines in the prevention of Marek's disease in chickens and in modifying the outcome of oncogenic herpesvirus infections in nonhuman primates offers hope of at least limited application of microbial vaccines in the prevention of human cancer.