Cancer is a disease of the DNA, and over 100 distinct forms are recognized, with each type having extensive heterogeneity. There are many agents that can lead to cancer in humans, and these are broadly considered either as voluntary (lifestyle choice such as diet, exercise, unsafe sex) or involuntary (ambient environment and the workplace). Since 1775 occupational exposures have been linked to cancer in humans, although it has only been in the past 50. years that significant data and tools to analyze that data have been available to unequivocally demonstrate causation. However, despite this rapid growth, the everyday causes of cancer remain largely elusive. This article will focus on those agents and mixtures that are known or strongly believed to be carcinogenic in humans that also have a significant human exposure risk. Problems with definitions and exposure assessment hinder epidemiological progress.