Brain immune privilege for many years overshadowed investigation of interaction between the nervous and immune systems. Over time, however, evidence of their interdependence has emerged. In the 1970s, as antibody-mediated autoimmunity was being defined, the neurological disorder myasthenia gravis was shown to be due to autoantibodies that could be passively transferred to mice and removed from humans by plasma exchange. In the 1980s, Fink and Weihe showed that neurons innervate lymph nodes, and from the 1990s onwards, Rothwell and colleagues observed the impact of soluble inflammatory mediators on behaviour. For example, in a key experiment, her team showed that systemic and intraventricular injection of IL-1 led to fever and reduced food motivation in experimental animals, interpreted as “sickness behaviour”; this technique is now used as a model for inflammation-driven depression. Furthermore, IFN- α was unexpectedly found to cause depression when given as a treatment for hepatitis C. More recently, diseases have been identified in which autoantibodies interfere with neuronal function and cause severe psychiatric symptoms, such as N-Methyl D-Aspartate Receptor (NMDAR)-antibody encephalitis. There is now emerging interest in the patho-aetiological role of the immune system in various severe mental illnesses, and the use of immunotherapies in their treatment.