Introduction: Insomnia is common among children and adolescents with Autism spectrum disorder (ASD). The first drug licensed for insomnia in this population, a pediatric-appropriate prolonged-release melatonin (PedPRM) formulation is described.Areas covered: Literature search on PedPRM efficacy and safety profile in clinical trials, and a proposed decision-making algorithm to optimize outcome in the treatment of insomnia in children and adolescents with ASD.Expert opinion: PedPRM treatment effectively improves sleep onset, duration and consolidation, and daytime externalizing behaviors in children and adolescents with ASD and subsequently caregivers' quality of life and satisfaction with their children's sleep. The coated, odorless and taste-free mini-tablets are well-accepted in this population who often have sensory hypersensitivity and problems swallowing standard tablet preparations. The most frequent long-term treatment-related adverse events were fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%) with no evidence of delay in height, BMI, or pubertal development, or withdrawal effects. The starting dose is 2 mg once daily independent of age or weight, escalated to 5-10 mg/day if predefined treatment success criteria are unmet. Slow melatonin metabolizers (~10% of children), may require lower doses. Given its long-term efficacy, safety and acceptance, PedPRM may ameliorate long-term consequences of insomnia in this population.