The search for new drugs to treat human disease is strongly reliant on the use of in vivo animal models to generate pre-clinical data. However, drug efficacy in experimental disease models does not often translate effectively to the human condition. Multiple sclerosis (MS) is a disease of the human central nervous system that has features duplicated in the animal model experimental autoimmune encephalomyelitis (EAE). Many compounds have shown activity in EAE and some have progressed to clinical trials in MS but only a small number of treatments have proved beneficial. This article describes compounds with dual activity in EAE and MS and considers the possible reasons for transference of drug effects from the model to the human disease. Prerequisites to ensure robust pharmacological efficacy in EAE are discussed with the aim of improving the success rate for pre-clinically active compounds being of benefit in the treatment of MS.