Tracheal intubation is performed frequently in the NICU and delivery room. This procedure is extremely distressing, painful, and has the potential for airway injury. Premedication with sedatives, analgesics, and muscle relaxants is standard practice for pediatric and adult intubation, yet the use of these drugs is not common for intubation in neonates. The risks and benefits of using premedications for intubating unstable newborns are hotly debated, although recent evidence shows that premedication for non-urgent or semi-urgent intubations is safer and more effective than awake intubations. This article reviews clinical practices reported in surveys on premedication for neonatal intubation, the physiological effects of laryngoscopy and intubation on awake neonates, as well as the clinical and physiological effects of different drug combinations used for intubation. A wide variety of drugs, either alone or in combination, have been used as premedication for elective intubation in neonates. Schematically, these studies have been of three main types: (a) studies comparing awake intubation versus those with sedation or analgesia, (b) studies comparing different premedication regimens comprising sedatives, analgesics, and anesthetics, and (c) case series of neonates in which some authors have reported their experience with a specific premedication regimen. The clinical benefits described in these studies and the need for pain control in neonates make the case for using appropriate premedication routinely for elective or semi-urgent intubations. Tracheal intubation without the use of analgesia or sedation should be performed only for urgent resuscitations in the delivery room or other life-threatening situations when intravenous access is unavailable.