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Despite advances in intensive care medicine and neurosurgical procedures, the mortality and long-term disability rates for serious traumatic and non-traumatic brain injuries remain high. With improvements in intensive care, the most common proximate cause of death in comatose patients following acquired brain injury is represented by the withdrawal of life-sustaining therapies (ABI). This procedure, however, raises serious ethical concerns, as current approaches in the prediction of consciousness recovery and functional independence lack accuracy. The prediction of neurological outcome after severe ABI at the individual patient level is variable and challenging. Current prognostication models applied in severe traumatic brain injury and the post-cardiac arrest population perform reasonably well in predicting the neurological outcomes in low-and high-severity patients but do not allow for accurate outcome predictions in patients with intermediate severity. The current review highlights new clinical and instrumental prognostication developments, with a particular focus on the prediction of consciousness recovery. In particular, recent research has leveraged neurophysiological techniques (electroencephalogram and somatosensory evoked potentials) to build a strategy for recovery prediction. In addition, we underline the relevance of instrumental motor assessments because motor impairment may affect the reliable evaluation of the effective consciousness level or may hamper patients’ complete functional recovery.