Epilepsy is a common neurological disorder that affects approximately 1% of the world’s pop7ulation. About one third of those patients suffer from treatment-resistant epilepsy (TRE8), defined as failure to stop seizures despite adequate trials of at least two medications at therapeutic dosages. There has been a growing interest in the development of novel antiepileptic drugs with different mechanisms of action. This narrative review, based on 42 references retrieved from Scopus and Medline, discusses the scientific data from human and animal studies regarding the efficacy of cannabis-based treatment for epilepsy. Benefits have been described in pre-clinical and clinical studies in children, but ongoing research will clarify the real role of cannabinoids in TRE.