It has long been known that individuals who are exposed to similar occupational conditions may experience very different health outcomes. Some of this variability may be due to concomitant exposures and lifestyle factors, but much of it is believed to be a function of differences in individual genetic susceptibility to the adverse consequences of workplace exposures. Attempts to understand this phenomenon began with small studies relating heritable variation in specific xenobiotic metabolizing enzymes to the risk of adverse effects due to occupational exposures. Many of the genetic risk factors identified in these early studies, however, turned out to make only small contributions to susceptibility and it subsequently became clear that it is necessary to examine genetic variation across the entire genome and relate it to lifestyle factors and environmental exposures as well as occupation if we are to explain complex occupational health conditions such as aromatic amine‐induced bladder cancer. Fortunately, the tools we need to do this are now available: genome‐wide association studies are becoming routine and large, well‐characterized population cohorts such as the UK Biobank provide an ideal setting for these investigations. We are now ideally placed to use these resources to define the genetic profiles which determine susceptibility, while the rapidly decreasing cost of genomic sequencing offers the prospect of preexposure screening to identify and protect workers who are likely to experience the adverse effects of workplace exposure.