The list of failed trials with ineffective or toxic drugs, despite encouraging data from research, is growing. Therapeutic trials in multiple sclerosis (MS) may be particularly vulnerable to fail because the pathogenesis of this disease is still not understood. Thus theoretically promising agents may paradoxically increase disease activity or be associated with unforeseen adverse effects. Short-term favourable trends may reverse with a prolonged follow-up. Antigen-specific therapies can stimulate in vivo rather than to inhibit encephalitogenic cells. In addition to the negative message of failed trials itself, they can promote new hypotheses about disease pathophysiology. Failed trials can provide valuable information how studies and outcome measures should be designed for future trials. So it is important that negative trials are published and available for the MS community.