It is becoming increasingly clear that genetic factors modify outcome after traumatic brain injury (TBI). The best known example of this is the association between the apolipoprotein E4 allele (APOE epsilon4) and poorer outcomes. However, our knowledge of the many other genes that might influence outcome is still in its infancy. This article will review the basic principles underlying recent advances in genetics, and then describe the current state of knowledge regarding the impact of genetic factors on TBI outcome. We conclude that although genetic advances have implications for prognosis, their biggest contribution will be to elucidate the pathophysiology of TBI, potentially leading to new treatments.