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Background: Severe traumatic brain injury (TBI) management begins in the pre-hospital setting, but clinicians are left with limited options for stabilisation during retrieval due to time and space constraints, as well as a lack of access to monitoring equipment. Bolus osmotherapy with hypertonic substances is commonly utilised as a temporising measure for life-threatening brain herniation, but much contention persists around its use, largely stemming from a limited evidence base. Method: The authors conducted a brief review of hypertonic substance use in patients with TBI, with a particular focus on studies involving the pre-hospital and emergency department (ED) settings. We aimed to report pragmatic information useful for clinicians involved in the early management of this patient group. Results: We reviewed the literature around the pharmacology of bolus osmotherapy, commercially available agents, potential pitfalls, supporting evidence and guideline recommendations. We further reviewed what the ideal agent is, when it should be administered, dosing and treatment endpoints and/or whether it confers meaningful long-term outcome benefits. Conclusions: There is a limited evidence-based argument in support of the implementation of bolus osmotherapy in the pre-hospital or ED settings for patients who sustain a TBI. However, decades’ worth of positive clinician experiences with osmotherapy for TBI will likely continue to drive its on-going use. Choices regarding osmotherapy will likely continue to be led by local policies, individual patient characteristics and clinician preferences.