Functional genomics involving genome-wide expression analyses is rapidly finding applications in clinical medicine. New technologies now permit the simultaneous analysis of mRNA levels for the entire human transcriptome from as few as 1000 cells. This approach is dramatically changing the way we define health and disease, allowing, for the first time, an unbiased view of the global changes in gene expression that are occurring. For the study of trauma biology and sepsis, this technology offers a powerful tool to develop molecular signatures for inflamed tissues and specific cell populations. At present, functional genomics is being used to classify the progress of disease and survival in response to traumatic and burn injury, sepsis and visceral ischemia, and reperfusion injury, as well as to describe patterns of gene expression in response to varying microbial pathogens. As the number of bioinformatics tools increases, functional genomics is beginning to reveal the underlying complexity of the biological response to a variety of inflammatory diseases and is providing new approaches for their exploration. Functional genomics is becoming a standard tool in inflammation research as a means to unravel the basic biological processes.