Polytrauma associated with traumatic brain injury (TBI) is defined as a concurrent injury to the brain and one or more body areas or organ systems that results in physical, cognitive, and psychosocial impairments. Consequently, polytrauma accompanied by TBI presents a unique challenge for emergency medicine, in particular, to those associated with the austere environments encountered in military theaters of operation and the logistics of en-route care. Here, we attempt to put needed focus on this medical emergency, specifically addressing the problem of an exsanguinating polytrauma requiring fluid resuscitation complicated by TBI. Critical questions to consider are the following: (1) What is the optimal resuscitation fluid for these patients? (2) In defining the resuscitation fluid, what considerations must be given with regard to the very specific logistics of military operations? and (3) Can treatment of the brain injury be initiated in parallel with resuscitation practices. Recognizing the immense clinical and experimental complexity of this problem, our goal was to encourage research that embraces with high-fidelity 'combined' animal models of polytrauma and TBI with an objective toward elucidating safe and effective neurotherapeutic resuscitation protocols.