Assays for pathogenic antibodies were first developed in the early 1970s. Little improvement was made in the accuracy of these test systems until the mid 2000s where our understanding of the importance of test substrate slowly shifted. At the same time the CNS was considered an immune privileged location where antibodies did not cause disease, but researchers at the Mayo Clinic led by Dr. Vanda Lennon demonstrated that antibodies to aquaporin-4 were present in people with a Multiple Sclerosis-like disease called Neuromyelitis optica. Antibodies (with complement) cause lesions in the optic nerve, spinal cord and brain. Over the following 15 years researchers at Pennsylvania (Dr. Dalmau), Barcelona (Drs Dalmau and Graus) and Oxford (Drs Vincent, Irani, Pettingill and I) identified 15-20 new antibody targets that are used in over 60 countries to support a clinical diagnosis of different CNS diseases. These tests are not available in developing countries. I will share what I have learnt during this exciting period when autoimmune neurology was established.