As an essential component of cellular defense against a variety of endogenous and exogenous stresses, nuclear factor erythroid 2-related factor 2 (Nrf2) has received increased attention in the past decades. Multiple studies indicate that Nrf2 acts not only as an important protective factor in injury models but also as a downstream target of therapeutic agents. Activation of Nrf2 has increasingly been linked to many human diseases, especially in central nervous system (CNS) injury such as traumatic brain injury (TBI). Several researches have deciphered that activation of Nrf2 exerts antioxidative stress, antiapoptosis, and antiinflammation influence in TBI via different molecules and pathways including heme oxygenase-1 (HO-1), NADPH:quinine oxidoreductase-1 (NQO-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2). Hence, Nrf2 shows great promise as a molecular target in TBI. In the present article, we provide an updated review of the current state of our knowledge about relationship between Nrf2 and TBI, highlighting the specific roles of Nrf2 in TBI.