Abstract Microglia have a variety of functions in the brain such as synaptic remodeling, damage repair of the central nervous system (CNS), and CNS’ inflammatory response to peripheral infections. The response depends on the type of insult and infection and includes a range of variety of activation states, the duration of which will decide the outcome. In response to traumatic brain injury (TBI), early activation can lead to early restoration of function, while prolonged and continuous activation can cause neurodegeneration states. Current evidence, however, states that this may not be the case. In this article, we discuss this seldom understood topic of microglia response to TBI, and analyze their distribution, function and possible sites of manipulation. Animal studies have allowed genetic and pharmacological manipulations of microglia activation, in order to define their role. Microglia activation can be remote to the site of injury, and thus their manipulation may play a significant role in the response to any trauma.