Background. Neonatal intubation is a stressful procedure that requires premedication to improve intubation conditions and reduce stress and adverse physiological responses. Premedication used during the INSURE (INtubation, SURfactant therapy, Extubation) procedure should have a very short duration of action with restoration of spontaneous breathing within a few minutes. Aims. To determine the best sedative for intubation during the INSURE procedure by systematic review of the literature. Methods. We reviewed all relevant studies reporting on premedication, distress, and time to restoration of spontaneous breathing during the INSURE procedure. Results. This review included 12 studies: two relatively small studies explicitly evaluated the effect of premedication (propofol and remifentanil) during the INSURE procedure, both showing good intubation conditions and an average extubation time of about 20 minutes. Ten studies reporting on fentanyl or morphine provided insufficient information about these items. Conclusions. Too little is known in the literature to draw a solid conclusion on which premedication could be best used during the INSURE procedure. Both remifentanil and propofol are suitable candidates but dose-finding studies to detect effective nontoxic doses in newborns with different gestational ages are necessary.