It has been estimated that 50% of human transcriptome, the collection of mRNA in a cell, is expressed in the brain, making it one of the most complex organs to understand in terms of genomic responses to injury. The availability of genome sequences for several organisms coupled with the increasing affordability of microarray technologies makes it feasible to monitor the mRNA levels of thousands of genes simultaneously. In this paper, we provide an overview of findings using both cDNA- and oligonucleotide-based microarray analyses after experimental traumatic brain injury (TBI). Specifically, the utility of this methodology as a means of cataloging the biochemical sequelae of brain trauma and elucidating novel genes or pathways for further study is discussed. Furthermore, we offer future directions for the continued evaluation of microarray results and discuss the usefulness of microarray techniques as a testing format for determining the efficacy of mechanism-based therapies.