Traumatic brain injuries (TBIs) account for the majority of injury-related deaths in the United States with roughly two million TBIs occurring annually. Due to the spectrum of severity and heterogeneity in TBIs, investigation into the secondary injury is necessary in order to formulate an effective treatment. A mechanical consequence of trauma involves dysregulation of the blood–brain barrier (BBB) which contributes to secondary injury and exposure of peripheral components to the brain parenchyma. Recent studies have shed light on the mechanisms of BBB breakdown in TBI including novel intracellular signaling and cell–cell interactions within the BBB niche. The current review provides an overview of the BBB, novel detection methods for disruption, and the cellular and molecular mechanisms implicated in regulating its stability following TBI.