Organ complications in end-stage renal disease (ESRD) such as cardiovascular disease, anemia, bone disease, malnutrition, inflammation, and infections occur in many organ systems and are caused by a multitude of underlying disease-, uremia-, and therapy-related factors, and with a wide range of manifestations and severity. Interindividual variability in the pathophysiologic response of the uremic host to environmental factors, including renal replacement therapy, may be governed to a significant degree by genetic susceptibility factors. Specific genes regulate the pathophysiologic responses of organ systems affected by ESRD and can serve as candidate genes for the host-environment interaction. This review summarizes emerging clinical and translational research work in the field of genetic polymorphism of candidate genes and their effects on the development of organ complications in ESRD. Methodologic limitations of the existing published data, the need for large prospective cohort studies, and potential future risks for the use of genomic information in resource allocation are also highlighted.