Autoimmune encephalitis is characterized by subacute onset of the altered mental status that can rapidly progress to autonomic instability and refractory seizures requiring intensive care. It is mediated by autoantibodies that bind to synaptic surface proteins and alter their function. In contrast to many autoimmune CNS diseases, there is often little detectable inflammatory damage to the brain making it difficult to diagnose. Early engagement of a multidisciplinary team is essential to obtaining a complete diagnostic workup and instituting definitive therapy as early as possible to optimize outcomes. Diagnosis, treatment, and monitoring for this devastating condition continue to evolve. Pathogenesis, diagnosis and both current and emerging therapies are reviewed.