Purpose: To determine the toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of cediranib administered orally, once daily, continuously in children and adolescents with solid tumors. Patients and Methods: Children and adolescents with refractory solid tumors, excluding primary brain tumors, were eligible. DLT at the starting dose of 12 mg/m2/d resulted in de-escalation to 8 mg/m2/d and subsequent re-escalation to 12 and 17 mg/m2/d. Pharmacokinetic and pharmacodynamic studies were performed during cycle 1. Response was evaluated using WHO criteria. Results: Sixteen patients (median age, 15 years; range, 8 to 18 years) were evaluable for toxicity. DLTs (grade 3 nausea, vomiting, fatigue in one; hypertension and prolonged corrected QT interval in another) occurred in patients initially enrolled at 12 mg/m 2/d. Subsequently, 8 mg/m2/d was well tolerated in three patients. An additional seven patients were enrolled at 12 mg/m2/d; one had DLT (grade 3 diarrhea). At 17 mg/m2/d, two of four patients had DLTs (grade 3 nausea; intolerable grade 2 fatigue). Non-dose-limiting toxicities included left ventricular dysfunction, elevated thyroid stimulating hormone, palmar-plantar erythrodysesthesia, weight loss, and headache. The MTD of cediranib was 12 mg/m2/d (adult fixed dose equivalent, 20 mg). At 12 mg/m2/d, the median area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) was 900 ng·h/mL, which is similar to adults receiving 20 mg. Objective responses were observed in patients with Ewing sarcoma, synovial sarcoma, and osteosarcoma. Conclusion: The recommended monotherapy dose of cediranib for children with extracranial solid tumors is 12 mg/m2/d administered orally, once daily, continuously. A phase II study is in development.