Environmental and occupational causes of cancer are defined as either physical or chemical agents in the workplace or general environment to which individuals are involuntarily exposed. This article reviews the state of the science for cancer sites that have been most strongly linked to environmental and occupational causes. The article also describes efforts to quantify the contribution of environmental and occupational exposures to the overall cancer burden, reviews the issue of cancer clusters and their contribution to the science, and details other lines of evidence that further justify the importance of preventing environmental and occupational causes of cancer.