Gamma Knife surgery (GKS) is a minimally invasive neurosurgical procedure, generally performed under moderate sedation along with local analgesia for fixation of a stereotactic frame to the patient’s head, and is managed mostly by nonanesthesiologists. There are some risks for respiratory function during GKS and definite specifics for its management, since the presence of the stereotactic frame may impede access to the patient’s airway and interfere with direct visual observation of him or her by medical personnel. Continuous monitoring for early detection of respiratory depression and timely intervention in the event of an emergency seem essential during radiosurgical procedures, but no relevant standards have been established to date. Since hypoventilation appears in advance of desaturation, sole monitoring of peripheral oxygen saturation (SpO2) by pulse oximetry is insufficient for detection of an early respiratory decline. According to the American Society of Anesthesiologists (ASA) practice guidelines for sedation and analgesia by nonanesthesiologists, the adequacy of ventilation during moderate and deep sedation should be evaluated by continuous observation of qualitative clinical signs and monitoring of end-tidal carbon dioxide (EtCO2). Overall, combined use of pulse oximetry and capnography may be recommended during GKS and may enhance its safety, especially in cases of medically fragile, uncooperative, or pediatric patients.