The vaccination against Humanpapilloma Virus (HPV) is an effective strategy to prevent high-risk HPV infection and subsequent cervical carcinogenesis. Although the safety profile has been ascertained, the relation with the development of central nervous system (CNS) autoimmune disorders (AD) appears still controversial. Multiple Sclerosis (MS) is the most common cause of chronic neurological impairment in young people, typically striking females. The main purpose of this review was to assess the association between HPV vaccination and MS.