Although the development of multiple sclerosis (MS) after idiopathic optic neuritis (ON) is well known, MS following ethambutol-induced ON is not widely recognized. We hypothesize the possible association between ethambutol-induced ON and MS based on empirical data of six patients with ethambutol-induced ON who progressed to MS. Whether there is a genuine link between ethambutol-induced ON and MS is unresolved, but our observations do raise the possibility. It is difficult to speculate on the mechanism for such a link, because the etiology of MS itself is unknown. It is possible that ethambutol or its metabolites induce an autoimmune response, through molecular mimicry or other phenomena, cross-reacting with central nervous system (CNS) myelin.