The typical complications of end-stage renal disease (ESRD) vary in frequency and severity. Whereas anemia of chronic kidney disease might require high doses of exogenous erythropoietin (EPO) in some individuals, others hardly ever need hormone replacement. The same observation can be made for immune defense functions in patients with ESRD. Our understanding of the functional consequences of genetic polymorphisms in a wide array of genes has recently gained momentum. In patients with ESRD, interindividual differences in anemia parameters have been linked in part to genetic polymorphisms. Indeed, although inflammation is an important predictor of the need for EPO, to date a link to cytokine gene polymorphisms has not been established. However, the need for EPO has been linked to polymorphisms in the angiotensin-converting enzyme (ACE) and vitamin D receptor genes. In contrast, in dialysis patients, interindividual variability in host immune responses, including nonspecific (bacterial) and antigen-specific (viral) immune mechanisms has been linked to variations in the interleukin-10 and myeloperoxidase genes as well as variability in human leukocyte antigens (HLAs). In conclusion, the role of genetic polymorphisms in predicting the development and severity of anemia in chronic kidney disease as well as host immune competence is in its infancy and warrants further inquiry.