The processes underlying autoimmune CNS inflammation are complex, but key roles for autoimmune lymphocytes seem inevitable, based on clinical investigations in multiple sclerosis (MS) and related diseases such as neuromyelitis optica, together with the known pathogenic activity of T cells in experimental autoimmune encephalomyelitis (EAE) models. Despite intense investigation, the details of etiopathology in these diseases have been elusive. Here we describe recent advances in the rodent models that begin to allow a map of pathogenic and protective immunity to be drawn. This map might illuminate previous successful and unsuccessful therapeutic strategies targeting particular pathways, whilst also providing better opportunities for the future, leading to tailored intervention based on understanding the quality of each individual's autoimmune response.