Patients with severe grades of life-threatening brain injury are commonly characterized as having devastating brain injury (DBI), which we have defined as: 'any neurological condition that is assessed at the time of hospital admission as an immediate threat to life or incompatible with good functional recovery AND where early limitation or withdrawal of therapy is being considered'. The outcome in patients with DBI is often death or severe disability, and as a consequence rapid withdrawal of life sustaining therapies is commonly contemplated or undertaken. However, accurate prognostication in life-threatening brain injury is difficult, particularly at an early stage. Evidence from controlled studies to guide decision-making is limited, and there is a risk of a 'self-fulfilling prophecy', with early prognostication leading to early withdrawal of life sustaining therapies and death. The Joint Professional Standards committee of the Faculty of Intensive Care Medicine and the Intensive Care Society convened a consensus group with representation from stakeholder professional organizations to develop clear professional guidance in this area. It recognized that the weak evidence base makes GRADE guidelines difficult to justify. We have made 12 practical, pragmatic recommendations to help clinicians deliver safe, effective, equitable, and justifiable care within resource constrained healthcare systems. In the situation where patient-centred outcomes are recognized to be unacceptable, regardless of the extent of neurological improvement, then early transition to palliative care is appropriate. These recommendations are intended to apply where the primary pathology is DBI, rather than where DBI has compounded a progressive and irreversible deterioration in other life-threatening comorbidities.