In spite of a huge number of reports of severe hazards after injection of hepatitis B vaccine (HBV), the issue is regularly raised that no mechanism is available for the development of central demyelinating disorders such as multiple sclerosis (MS). A number of convergent facts, however, suggests that the manufacturing process could introduce HBV polymerase as a contaminant, and then trigger an auto-immune process against myelin in some vaccinated subjects. Of great significance, this hypothesis is likely to give the missing link to account for the considerable body of clinical and epidemiological evidence documenting that, for a drug used with a preventive purpose, HBV has an unusual potential to induce central neurological disorders amongst others unwanted side-effects.