The apnea test is a mandatory examination for determining brain death (BD), because it provides an essential sign of definitive loss of brainstem function. However, several authors have expressed their concern about the safety of this procedure as there are potential complications such as severe hypotension, pneumothorax, excessive hypercarbia, hypoxia, acidosis, and cardiac arrhythmia or asystole. These complications may constrain the examiner to abort the test, thereby compromising BD diagnosis. Nevertheless, when an appropriate oxygen-diffusion procedure is used, this technique is safe. We review here the prerequisites to begin the test, its procedure, potential complications, and the use of alternative ancillary tests. We recommend that the apnea test be retained as a mandatory procedure for the diagnosis of BD. In those situations when the apnea test is terminated by the examiner for some reason or when it is impossible to carry it out in a patient due to the presence of some pathologic condition, alternative ancillary tests should be used to confirm BD.