High-throughput techniques, such as genome-wide scans, will allow genotyping of a large number of single-nucleotide polymorphisms throughout the human genome. There is intense interest to apply this technology to understand genetics of complex traits, including severe sepsis. To effectively utilize this technology, large cohorts of septic patients will have to be recruited. Careful attention should be paid to different aspects of study design and analyses as large, multicenter cohorts are assembled for genome-wide association studies.