Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology. Immune cells respond to acute signals from damaged cells, initiate neuroinflammation, and drive the pathological consequences over time. Importantly, the mechanism(s) of injury, the location of the immune cells within the brain, and the animal species all contribute to immune cell behavior following traumatic brain injury. Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration. Within this paper, we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury.