Because of their high prevalence in the general population, genetic variants that determine susceptibility to environmental exposures may contribute greatly to the development of occupational diseases in the setting of specific exposures occurring in the workplace. Studies investigating genetic susceptibilities in the workplace may: (1) provide mechanistic insight into the aetiology of disease, in particular the determination of environmentally responsive genes; (2) identify susceptible subpopulations with respect to exposure; and (3) provide valuable input in setting occupational exposure limits by taking genetic susceptibility into account. Polymorphisms in the NAT2 and the HLA-DPB1Glu69 genes provide classic examples of how genetic susceptibility markers have a clear role in identifying disease risk in bladder cancer and chronic beryllium disease, respectively. For diseases with more complex and multifactorial aetiology such as occupational asthma and chronic airways disease, susceptibility studies for selected genetic polymorphisms provide additional insight into the biological mechanisms of disease. Even when polymorphisms for genetic susceptibility have a clear role in identifying disease risk, the value of wide scale genetic screening in occupational settings remains limited due to primarily ethical and social concerns. Thus, large scale genetic screening in the workplace is not currently recommended.