•This review examines the role of HHV-6 infection in epilepsy.•HHV-6 infection has been linked with febrile seizures, TLE and encephalitis.•We discuss potential mechanisms of neuroinflammation linked to HHV-6 infection. Infection with Human Herpesvirus-6 (HHV-6) has been associated with different epilepsy syndromes, including febrile seizures and status epilepticus, acute symptomatic seizures secondary to encephalitis and temporal lobe epilepsy. This neurotropic DNA virus is ubiquitous and primary infection occurs in up to 80% of children by age two years. While two viral variants have been identified, HHV-6B is the one that has been primarily linked to disease in humans, including epilepsy. After initial viremia, the virus can establish chronic latency in brain tissue, peripherally in tonsils and salivary glands and infect several different cell lines by binding to the complement regulator CD-46. In this review we will focus on discussing the evidence linking HHV-6 infection to different epilepsy syndromes and analyzing proposed pathogenic mechanisms.