Pharmacological treatment of traumatic brain injury (TBI) is complex and still in its infancy as a field of clinical investigation. Patients with TBI have a wide variety of central nervous system (CNS) problems as well as numerous peripheral disorders that can be addressed pharmacologically. This chapter focuses on the medications that are used to alter neurological or behavioral functions, neurotransmission in the autonomic nervous system and the drugs that modify it. One must be cognizant of the potential and often confounding interactions of pharmacotherapy targeting a neurotransmitter in one functional system, such as dopamine (DA) in the striatum for Parkinson's disease with 'unintended' targets in the limbic and cortical DA systems. Acetylcholine (ACh) is one of the most widely studied neurotransmitters and one of the oldest, phylogenetically. It was, in fact, the neurotransmitter for which chemical neurotransmission was originally demonstrated when it was found to be released from nerves innervating the frog heart by Loewi in 1921.