Initial use of alemtuzumab in multiple sclerosis (MS) was in patients with secondary progressive disease. Just as the efficacy experience of alemtuzumab generated some novel concepts of MS biology, such as the possibility of neuroprotective autoimmunity, so too has exploration of its adverse effects. The most significant adverse effect of alemtuzumab is secondary autoimmunity. A straightforward conclusion from the experience of using alemtuzumab, both open-label and within trials, is that it has the potential to be one of the most efficacious treatments of MS to date. A key lesson from the history of alemtuzumab treatment of MS has been that the disease is only vulnerable to such anti-inflammatory treatments early in its course, before the conditions that predispose to neurodegeneration, and secondary progression, have been set up. The finding of disability improvement after alemtuzumab suggests a new treatment paradigm in MS. There is no signal that alemtuzumab causes neoplasia.