The proper use of psychopharmacologic agents in the management of traumatic brain injury (TBI) is not clearly developed. Although the potential for significant amelioration of post-TBI deficits exists through pharmacologic interventions, major deficits persist regarding relative indications, efficacy, and side effects. Extensive reliance upon these agents, primarily for behavior control, is common despite clinical indications of marginal or unknown validity. Various clinical, administrative, and economic forces tend to accentuate the use of psychopharmacologic agents and create potential conflicts of interest for prescribing physicians. The single-case methodology is an appropriate approach to these difficult clinical exigencies. Legal precedent from traditional psychiatric experience suggests legal guidelines for use of these agents in management of TBI. Failure to adhere to these may expose clinicians to liability.