Since mechanisms of action of the approved therapies for multiple sclerosis (MS) involve anti-inflammatory effects, and since these treatments result primarily in a reduction in relapse rates, it is logical to hypothesize that mechanisms of action of the protective effect of pregnancy on MS relapses involve anti-inflammatory effects. Two estrogens (estradiol and estriol) and progesterone each increase progressively during pregnancy. Levels of estrogens that are in oral contraceptives or hormone replacement therapy may not be high enough to be protective in MS. Numerous factors other than sex hormones have been identified in sera during pregnancy and have been shown to be immunosuppressive either in cultures of immune cells in vitro or in experimental autoimmune encephalomyelitis (EAE) models. The combined anti-inflammatory and neuroprotective state of pregnancy, perhaps aimed at protecting the fetus, may be precisely what is needed to protect the central nervous system (CNS) of a mother with MS.