Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. Present therapeutic strategies for MS reduce inflammation and its destructive consequences, but are not effective in the progressive phase of the disease. There is a need for neuroprotective and restorative therapies in MS. Insulin-like growth factor-1 (IGF-1) is of considerable interest because it is not only a potent neuroprotective trophic factor but also a survival factor for cells of the oligodendrocyte lineage and possesses a potent myelinogenic capacity. However, the IGF system is complex and includes not only IGF-1 and IGF-2 and their receptors but also modulating IGF-binding proteins (IGFBPs), of which six have been identified. This chapter provides an overview of the role of the IGF system in the pathophysiology of MS, relevant findings in preclinical models, and discusses the possible use of IGF-1 as a therapeutic agent for MS.