Multiple sclerosis (MS), the most important human inflammatory demyelinating disease of the central nervous system, is characterized by various clinical disease courses, inhomogeneous and unpredictable therapeutic effects, heterogenous genetic backgrounds and immunopathogenetic subtypes as demonstrated by neuropathology. Because of this heterogeneity of MS, a subtyping of our patients by genetical, clinical, neuroradiological, and neuroimmunological parameters will be necessary in the future. Therefore the importance of identifying biological markers for MS has evolved over the past years. Evidence for a possible role of antibodies as biological markers for MS comes from several studies indicating that intrathecal antibody production and the dominance of B cells are associated with a more progressive disease course. In this review we will give an overview on the current status and potential applicability of antibodies as biological markers for the diagnosis, classification, disease activity and prediction of clinical courses in MS. We will therefore summarize the findings on autoantibodies to myelin and nonmyelin antigens and on viral antigens in MS. We believe that antibodies serving as biomarkers will help to establish a differential therapeutic concept in MS, which will allow to treat individuals selectively according to their pathogenetic subtype and disease status.