A large real-world study has found that cannabidiol (CBD), including off-label use, can significantly reduce seizures and improve daily functioning in children with drug-resistant epilepsy, with benefits persisting for more than a year. The prospective trial, published in the European Journal of Neurology, followed 103 pediatric patients treated at a tertiary center over a two-year period. Nearly half had conditions approved for CBD treatment such as Dravet syndrome, Lennox–Gastaut syndrome, or tuberous sclerosis, while the majority used it off-label for other forms of epilepsy. Our findings also emphasize the critical role of caregivers’ involvement in treatment evaluation, especially for pediatric patients with intellectual disability. By integrating parental input, clinicians can better assess a child’s response to CBD beyond seizure control, capturing more comprehensive improvements in emotional and behavioral functioning.