The aim of this study is to determine the extent of use of medications that have not been specifically licensed for use in children (unlicensed), or medications whose use is not in accordance with the conditions of their license (off-label), in neonates in a neonatal intensive care unit (NICU). Medications given to 105 neonates were prospectively reviewed every 2 weeks during a 4-month period. The assessment as to whether every medication prescribed was unlicensed or off-label for use in children was based on a number of reference sources. Five hundred and twenty-five series of medications were used, of which 310 (59%) were off-label and 87 (16%) were unlicensed. Ninety-eight neonates (93%) received at least one off-label medication. The major reason for prescribing off-label medications was a deviation from the recommended dosage or age of the patient. The reason for giving unlicensed medications was changes in the formulation of the medication. The use of off-label and unlicensed medications is common in neonates. In view of the gravity and problematic nature of the issue, international consensus is evolving to conduct clinical trials in neonates and infants, with regard to medications already on the market, and new medications.