The goal of this paper is to provide a systematic overview of literature regarding the differential diagnosis of brain death. Brain death is defined as the irreversible loss of all functions of the brain, including the brainstem. The three essential findings in brain death are coma, absence of brainstem reflexes, and apnea. An evaluation for brain death should be considered in patients who have suffered a massive, irreversible brain injury of identifiable cause. A patient determined as brain dead is legally and clinically dead. It is necessary to emphasize the importance of timely and accurate diagnosis of brain death, by excluding conditions that mimic brain death. In this review are presented conditions that can mislead and thus lead to uncertainty and delays in making a proper diagnosis of brain death. Locked-in syndrome is a catastrophic result of an infarction of the upper part of the pons cerebri, in which the patient is fully aware of everything, but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body, except for vertical eye movements. Fulminant GBS, a condition that can rapidly progress to a brain death - like state in just a few days where, if no reversibility is established, it can leave permanent consequences for the patient. Deep hypothermia is the most impressive condition that mimics brain death, with temperatures below 28 ° C, where all the reflexes of the brain stem are lost. Barbiturates overdose and other CNS depressants intoxications are a common cause of confusion in the diagnosis of brain death. Therefore, today, toxicological screenings are mandatory when diagnosing comatose patients. Akinetic mutism, a state of deep apathy, with conserved consciousness, but weak and slow voluntary movements, is different from brain death and an instrumental test such as EEG can clearly prove that such a patient is not brain dead. The importance of excluding conditions that mimic brain death lies in the possibility of organ donation from brain dead patients (DBD protocol). Although medicine is progressing and making maestral discoveries, the demand for organs continues to exceed the bid.