Clinical examination is paramount for prognostication in patients who are comatose after resuscitation from cardiac arrest. At 72 hours from recovery of spontaneous circulation (ROSC), an absent or extensor motor response to pain (M ≤ 2) is a very sensitive, but not specific predictor of poor neurologic outcome. Bilaterally absent pupillary or corneal reflexes are less sensitive, but highly specific predictors. Besides the clinical examination, investigations such as somatosensory evoked potentials (SSEPs), electroencephalography (EEG), blood levels of neuron-specific enolase (NSE), or imaging studies can be used for neuroprognostication. In patients who have not been treated using targeted temperature management (TTM), the 2006 Practice Parameter of the American Academy of Neurology suggested a unimodal approach for prognostication within 72 hours from ROSC, based on status myoclonus (SM) within 24 hours, SSEP, or NSE at 24 to 72 hours and ocular reflexes or M ≤ 2 at 72 hours. The 2015 guidelines from the European Resuscitation Council and the European Society of Intensive Care Medicine suggest a multimodal prognostication algorithm, to be used in both TTM-treated and non-TTM-treated patients with M ≤ 2 at ≥ 72 hours from ROSC. Ocular reflexes (pupillary and corneal) and SSEPs should be used first, followed by a combination of other predictors (SM, EEG, NSE, imaging) if results of the first predictors are normal.