An association between certain vaccinations and onset or relapse of multiple sclerosis (MS) has been debated. Based on PubMed, we made a thorough literature review and included all relevant studies, 51 on MS and 15 on optic neuritis (ON). Case studies were excluded. With the exception of a live vaccine against yellow fever, vaccinations appear safe in untreated patients with MS and ON. However, most studies were underpowered, and small risks cannot be excluded. One study of BCG vaccination after the first demyelinating event showed even a reduced risk of developing MS. Further studies are needed to fully exclude a causal association.