With the landmark publication of the human genome sequence and its subsequent division into haplotype blocks, the characterization of genetic variations is becoming a feasible approach to study both the pathophysiology and risk factors of complex traits. A number of strategies are available today for identifying candidate genes or polymorphisms associated with pertinent phenotypes. For Mendelian diseases with high penetrance owing to mutations in a single gene, such as polycystic kidney disease, linkage studies have been very successful in mapping the disease loci owing to the availability of families with multiple affected members. In contrast to monogenic conditions, complex diseases such as end-stage renal disease (ESRD) and complex traits such as individual variations in membrane transport and complications during the course of peritoneal dialysis (PD) therapy have a number of competing determinants and inhibitors, both genetic and environmental. Current results reflect this complexity, with few studies showing a large effect of any single risk factor on survival or outcome on PD. However, these studies have so far been small (less than 500 patients) and have not utilized bioinformatics or novel technologies (e.g., multiplex genotyping equipment). In the following review, we outline current approaches for using genetic data in clinical studies as well as highlight some of the most promising results in ESRD patients, particularly those on PD.