Over the last 20 years it has become clear that autoantibodies to neuronal or glial surface membrane proteins can cause central nervous system (CNS) disease. The patients usually present with seizures, cognitive and psychiatric disturbance and movement disorders, which are collectively termed “autoimmune encephalitis” to distinguish from those patients who have an infectious form of encephalitis. The autoimmune disorders present over days or weeks and progress rapidly, often requiring treatment in intensive care facilities. Importantly, these patients can make substantial recoveries when treated with immunotherapies that reduce antibody levels and immune cell activation. The main targets for the autoantibodies are membrane receptors and ion-channel related proteins. (a) Autoantibodies to the NMDA receptor (NMDAR) are found (in serum and CSF) in children and younger adults with seizures, behavioural and cognitive disturbance; the patients can progress to develop complex movement disorders, autonomic instability and loss of consciousness. Ovarian tumours that express the NMDAR are found in about 30% of females. Treatment with combinations of steroids, plasmapheresis, intravenous immunoglobulins are typical; anti-CD20 therapeutic antibodies or cyclophosphamide are used in severe cases. Recovery is often slow but can be impressive with return to normal life. (b) A distinct form of “limbic encephalitis” is associated with antibodies to LGI1. This protein regulates the activity of voltage gated potassium channels and AMPA receptors at CNS synapses, particularly in the limbic system. Anterograde memory loss is severe and seizures can be resistant to anti-epileptic medication. The cognitive problems can be preceded by a distinct seizure type called facio-brachial dystonic seizures and immunotherapies at this stage may prevent development of the full limbic encephalitis. CASPR2 is another protein that associates with potassium channels both in the CNS and at the axonal juxtaparanodes. CASPR2 antibodies are also found in limbic encephalitis but more specifically in patients with insomnia and peripheral nerve hyperexcitability, known as Morvan’s syndrome. Lung cancers and thymomas are found in a minority of these patients. (c) Antibodies to inhibitory GABA receptors are, not surprisingly, often associated with seizures and cognitive problems. Glycine receptor antibodies are rare but can cause not only muscle rigidity and exaggerated reflexes but also life-threatening respiratory failure due to involvement of the brainstem. The clinical syndromes associated with these and other antibodies are now widely recognised and immunotherapies used with successful outcomes. In vitro studies have demonstrated some of the mechanisms by which the antibodies interfere with function, and the diseases can be partially reproduced in mice by injection of patients’ purified or monoclonal antibodies. The lecture will show videos of typical patients and describe briefly some of the experiments performed by ourselves and others, drawing attention to the range of activities in this exciting field and to the many challenges and unanswered questions.