With the increasing survival of patients with traumatic brain injury (TBI), there is a growing recognition of the severity and heterogeneity of associated cognitive problems. Cognitive impairments ranging from arousal and attentional decrements to memory problems and various disorders of speech and language provide significant obstacles to the ongoing rehabilitation effort. One approach to ameliorating cognitive deficits is to intervene pharmacologically in an effort to effect symptomatic change via neurochemical alteration. In this review we discuss the therapeutic rationale and use of various classes of drugs including stimulants, dopaminergic agents, cholinergic agents, and antidepressants for the cognitive deficits that are apparent within a wide range of patients with acquired brain injury. A thorough review of literature pertaining to TBI is emphasized while necessarily including some studies from other populations. Recommendations based on findings within the literature are suggested as well as an overview on clinical use and monitoring of individual agents.