Current prediabetes screening relies mainly on immunologic markers. Genetic screening through HLA typing, which is used in families of affected patients, allows a stratification of risk levels according to the number and nature of alleles shared with the proband. Incomplete penetrance and the polygenic nature of susceptibility currently limit our ability to predict the disease with genetic markers. In addition, genetic factors can affect several aspects of the disease process, including insulin secretory capacity. This paper discusses the present and potential roles of genetic markers in prediabetes screening and briefly considers their use in the context of prevention trials.