Traumatic brain injury is a leading cause of mortality and long-term morbidity, particularly affecting young people. With our best therapies, one half of the patients with severe traumatic brain injury are never capable of living independently. Two interventions, which have real potential to improve neurological outcomes in patients with traumatic brain injury, are (i) very early induction of prophylactic hypothermia and (ii) exogenous erythropoietin therapy. There is substantial experimental evidence, a plausible biological rationale, and supportive clinical evidence from clinical trials to suggest a possible beneficial effect of prophylactic hypothermia and also for exogenous erythropoietin therapy in severe traumatic brain injury. Despite the recent guidelines and publications recommending these interventions, critical care clinicians should be conservative towards implementing these therapies outside clinical trials due to substantial efficacy and safety concerns. Nevertheless the high morbidity and mortality associated with severe traumatic brain injury (TBI) demands that we investigate the safety and efficacy of these promising potential therapies as a matter of urgency.