Hypothermia is widely accepted as the gold-standard method by which the body can protect the brain. Therapeutic cooling--or targeted temperature management (TTM)--is increasingly being used to prevent secondary brain injury in patients admitted to the emergency department and intensive care unit. Rapid cooling to 33 °C for 24 h is considered the standard of care for minimizing neurological injury after cardiac arrest, mild-to-moderate hypothermia (33-35 °C) can be used as an effective component of multimodal therapy for patients with elevated intracranial pressure, and advanced cooling technology can control fever in patients who have experienced trauma, haemorrhagic stroke, or other forms of severe brain injury. However, the practical application of therapeutic hypothermia is not trivial, and the treatment carries risks. Development of clinical management protocols that focus on detection and control of shivering and minimize the risk of other potential complications of TTM will be essential to maximize the benefits of this emerging therapeutic modality. This Review provides an overview of the potential neuroprotective mechanisms of hypothermia, practical considerations for the application of TTM, and disease-specific evidence for the use of this therapy in patients with acute brain injuries.