It is now widely accepted that genetic variation is a major contributor to the interindividual variability in susceptibility to and outcome of disease. While the genetic cause of many rare Mendelian disorders has been ascertained, the role genetic variation plays in the pathogenesis of complex diseases that are the result of multiple genes, multiple biological pathways, and environmental factors (eg, infection) are just beginning to be understood. In this issue, Sutherland et al present their finding of an association of haplotype clades of the interleukin 6 gene with increased 28-day mortality in critically ill adults with systemic inflammatory response syndrome (SIRS). Interleukin 6 is a key proinflammatory cytokine in the pathogenesis of SIRS, and increased levels of interleukin 6 have been associated with fatal outcome in SIRS and sepsis. Associations of genetic variation with outcome from SIRS and sepsis will provide valuable insight into interindividual variability in the response to inflammatory stimuli, which could eventually lead to diagnostic tests to predict outcome. Therapy targeted to individuals at high risk by genotype for an excessive inflammatory response and poor outcome could vastly improve survival and quality of life. Patient-tailored therapy of complex disease is one promise of the human genome project.