Multiple sclerosis (MS) has nowadays developed in the human population, and according to the existing evidence, the main cause is not well understood. In addition to the genetic factors, scientists propose the infections like other autoimmune diseases as the strong environmental hypothesis. By the last decade, microorganisms were supposed neglected in autoimmune disorders. Staphylococcus aureus has been recognized as an exacerbating agent in the development of MS. The various virulence factors enable this bacterium to cause complications from a mild skin infection to life-threatening meningitis and septicemia. Although there are not enough comprehensive studies about the role of microorganisms and MS, the reports reveal that microbial components presumably induce the auto reactions in the cells and antibody production. On the other hand, these interactions occur either in healthy individuals. Surveys also suggest no specific microorganism as the etiologic agent for MS, and other bacteria (Chlamydia pneumoniae), viruses (Herpesviridae and Retroviridae) are also involved. Until now, many investigations have been conducted to find out the MS triggering, progression, and other influencing factors, however, decoding the main contributor is not completely elucidated. The current review assesses the role of Staphylococcus aureus as the well known bacterial candidate in MS incidence.