The function of hormones has expanded to include immunomodulation and neuroprotection in addition to their classic roles. The story of how hormones influence inflammation and neuron and glial function is being slowly unraveled. There is increasing evidence that estrogen, progesterone, and testosterone contain immune responses and influence damage repair in the nervous system. Hormones such as prolactin and vitamin D are being explored as immunomodulators and may influence diseases such as multiple sclerosis (MS) or may be used therapeutically to modulate the immune response. More recently identified hormones, such as leptin and gherlin, may also influence the course of disease. This chapter reviews some of the evidence that supports a role for hormones in MS.