Experimental autoimmune encephalomyelitis (EAE) is a spectrum of neurological disorders in laboratory animals that is used to model multiple sclerosis (MS). However, few agents have translated from efficacy in EAE to the treatment of human disease. Although this may reflect species differences in pathological disease mechanisms, importantly it may also relate to the practice of how drugs and models are currently used. This often bears very little resemblance to the clinical scenarios where treatments are investigated, such that lack of appreciation of the biology of disease may doom drugs to failure. The use of EAE is critically appraised with the aim of provoking thought, improving laboratory practise and aiding researchers and reviewers to address quality issues when undertaking, reporting and interpreting animal studies related to MS research. This is important as many researchers using EAE could and should do more to improve the quality of the studies.