Epilepsy is defined as the presence of at least two unprovoked (or reflex) seizures occurring more than 24 hours apart or one unprovoked (or reflex) seizure with evidence of at least 60% recurrence risk. Despite the availability of newer antiseizure medications (ASMs), approximately 30% of persons with epilepsy continue to have uncontrolled seizures. Indeed, there is clear need for additional safe and effective epilepsy therapies. Since the ancient civilizations, cannabis has been used as a treatment for various ailments, including seizures. In the past two decades, there has been increasing anecdotal evidence of cannabis use for the treatment of epilepsy. More recently, randomized, placebo-controlled trials have demonstrated the efficacy and safety of adjunctive therapy with the pharmaceutical-grade of highly purified cannabidiol (CBD), derived from Cannabis sativa L., for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex (TSC). In this chapter, we provide an overview of cannabis history in the treatment of seizures and the clinical use of pharmaceutical-grade CBD (Epidiolex®) in the treatment of children and adults with rare and severe pediatric-onset epilepsies.