Hashimoto’s encephalopathy is an uncommon neurological condition associated with Hashimoto’s thyroiditis and is characterized by altered mental status, confusion, hallucinations, delusions, and sometimes seizures, in association with high serum anti-thyroid antibody concentration that is usually responsive to glucocorticoid therapy. It is sometimes referred to as a “neuro-endocrine disorder,” although the condition’s relationship to the endocrine system is widely disputed. Hashimoto’s encephalopathy has also been known by the following alternative names: steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), non-vasculitic autoimmune meningo-encephalitis (NAIM), and encephalopathy associated with autoimmune thyroid disease (EAATD). Hashimoto’s encephalopathy is most often characterized by a subacute onset of confusion with altered level of consciousness, seizures, and myoclonus. In contrast to the cognitive dysfunction associated with hypothyroidism or hyperthyroidism, Hashimoto’s encephalopathy is believed to be an immune-mediated disorder rather than representing the direct effect of an altered thyroid state on the central nervous system. Symptoms sometimes resolve themselves within days to weeks, leaving a patient undiagnosed. For many other patients, the condition may result in ongoing problems with a variety of manifestations, often confusing clinicians due to the diffuse nature of symptoms. Diagnosis requires the exclusion of other causes of encephalopathies and encephalitis including autoimmune encephalitis associated with neuronal surface antibodies and para-neoplastic ones. Diagnosis also is dependent on the demonstration of thyroid autoantibodies in serum. The majority of patients with Hashimoto’s encephalopathy respond to steroids or immune-suppressant treatment. This chapter discusses the epidemiology, pathogenesis, pathology, clinical presentation, investigations, differential diagnosis, treatment, and prognosis of Hashimoto’s encephalopathy.