Multiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity of clinical presentation as well as radiological and pathological findings. Although its etiology still remains unknown, the last decade has generated considerable success in understanding the underlying pathophysiology of MS. In addition to its view as a prototypic inflammatory autoimmune disorder, recent data support the importance of primary and secondary neurodegenerative mechanisms such as oligodendrocyte death, axonal loss and ion channel dysfunction. The deepened understanding of the immunopathogenesis as well as the limited effectiveness of the currently approved disease modifying therapies have led to a tremendous number of trials investigating potentially new drug targets. Emerging treatments take into account the different immunopathological mechanisms as well as strategies to protect against axonal damage or to promote remyelination. This review provides a compilation of novel immunotherapeutic strategies or new aspects of known immunotherapeutic agents which have evolved recently. The pathogenetic rationale of these novel drug targets for the treatment of MS as well as accompanying preclinical and clinical data are highlighted.