The impact of modern medical techniques has given rise to an increasing survival of persons with disorders of consciousness including coma, the vegetative state, and the minimally conscious state. The numbers of pediatric and adolescent survivors of brain injury who remain vegetative or minimally conscious are not definitively known, and while these patients have received growing professional consideration, no specific standards of care exist. Pediatric and adolescent treatment recommendations are not differentiated from adult populations although some questions linger regarding the progression and outcome of the disorders in adults as compared to those in children. Kluge Children's Rehabilitation Center has initiated a Low Response and Treatment Protocol for Children Following Acquired Brain Injury to provide structure for diagnostic and therapeutic initiatives. Its single subject design is literature based, empirically driven, and peer recognized. Clinical classifications label a patient's emergence from coma as uncomplicated, complicated by confounding medical conditions, or neuropathic complicated emergence. Patients receiving the neuropathic designation are considered for pharmacological intervention. Beyond optimizing care for the enrolled patient, the protocol is established to provide (Giacino, 1995) an ongoing data store for future group analysis. Case 1 presents the course of treatment and recovery for a 16-year-old male, severely disabled due to an automobile accident. Medical complications are addressed and his failure to progress is deemed complicated neuropathic at 14 weeks post-injury. At 15 weeks post-injury, administration of Amantadine 100 mg bid shows improvements, with almost complete emergence after two weeks at an increased dose of 200 gm bid. Discontinuation at the family's request, approximately a year post-injury, is followed by a measurable loss of functional ability. The patient regained functioning after returning to the Amantadine schedule. Case 2 outlines the course of treatment and recovery for a nine-year-old boy, the victim of a near drowning. Investigation considerations influence the structure of the protocol and analysis of its results. While first a therapeutic tool based on single subject design, the protocol attempts to qualitatively manage various threats to establishing causal relationships between drug interventions and the noted outcomes. Systematic consideration of the single subject design for therapeutic benefit, as well as making a meaningful contribution to the existing evidence base, is suggested until class I evidence is compiled to produce well supported standards of care. Copyright © 2000 John Wiley & Sons, Ltd.