Neurosurgical challenges after traumatic brain injury are often related to subacute phase complications and cranioplasty. The most common subacute phase complications are the syndrome of the trephined, post-traumatic hydrocephalus and post-traumatic fistulae. All these conditions have targeted surgical interventions, but patient selection and timing of interventions remain somewhat debatable. Moreover, in the context of cranioplasty, there is still no clear consensus regarding the most appropriate material to be used. In this chapter, neurosurgical challenges of the subacute phase of traumatic brain injury are reviewed and discussed.