The paper reviews selected aspects of progress and setbacks in cancer risk assessment and prevention during the four decades since the founding in 1947 of the Institute of Environmental Medicine at the New York University Medical Center. The period has been marked by substantial gains in quantifying the risks posed by exposure to known human carcinogens such as tobacco and ionizing radiation. By contrast, the search for sensitive and specific laboratory screens for human carcinogens has met setbacks, and epidemiological data still are needed to monitor the adverse effects of environmental exposures. The determination of acceptable levels of exposure to potential human carcinogens remains a formidable task, one for which no scientific framework yet exists. Future challenges in cancer risk assessment include the validation and use of biological markers of exposure and effective monitoring of risk among exposed populations. Future challenges in cancer prevention include the elimination of tobacco consumption and the acquisition of knowledge needed to prevent nutritionally and hormonally related cancers such as cancers of the bowel, prostate, and breast.