CONTEXT: Off-label and unlicensed use of drugs is a widespread practice in pediatric care because of the lack of specific efficacy and safety data and the absence of formulations adapted to the needs of these individuals. Pediatric patients with a life-limiting illness frequently receive drugs under these conditions, although no studies have established the prevalence of this practice. OBJECTIVES: To describe the prevalence, indications, and most common uses of off-label and unlicensed drugs in a pediatric palliative care unit (PPCU). METHODS: A prospective cross-sectional observational study carried out between January and October�2019. RESULTS: About 85 patients involving 1198 prescriptions were analyzed. A total of 39.6% were off label, and 12.9% were unlicensed. All received at least one off-label drug, with a median of five per patient (interquartile range 3-7), and 81.2% received at least one unlicensed drug. A total of 36.1% of the prescriptions were considered off label because of indication, 33.8% because of dosage, and 26.6% because of age. The main drugs used off label were oral morphine, oral levetiracetam, inhaled albuterol, sublingual ondansetron, oral tizanidine, sublingual fentanyl, and oral diazepam. The main symptoms treated with off-label drugs were dyspnea, pain, and nausea/vomiting. CONCLUSION: More than half of the prescriptions in this PPCU were off label or unlicensed. Treatment indication was one of the main reasons for off-label use. Administration of compounded preparations was common in patients with a life-limiting illness.