The influence of pregnancy on multiple sclerosis (MS) has long been a matter of controversy. Women with MS were often discouraged to consider pregnancy. The PRegnancy In Multiple Sclerosis (PRIMS) study was the first large prospective study aimed at assessing the possible influence of pregnancy and delivery on the clinical course of MS. Two hundred and fifty-four women with the diagnosis of MS were included during pregnancy and followed until the end of the second year post partum. The results were a reduction in the relapse rate during pregnancy, in comparison to the year before pregnancy, especially marked in the third trimester, and a significant increase in the relapse rate in the first trimester post partum. Starting in the second trimester post partum, the relapse rate did not significantly differ from the pre-pregnancy rate. About one third of the women experienced a post partum relapse. Pregnancy did not influence disability progression. Women with greater disease activity in the year before and during pregnancy had a higher risk of relapse in the first three months post partum. Neither breastfeeding, nor epidural analgesia correlated with the presence of a post partum relapse. When comparing predicted and observed status, 72% of the women were correctly classified by the multivariate model; it therefore seems unwise to use such a model to select women who would benefit from a putative preventive therapy. The PRIMS study had other major consequences: it fostered the development of specific therapeutic strategies to prevent post partum relapses (i.v. immunoglobulins, i.v. methylprednisolone), and suggested a potential role for sex hormones in the natural history of MS during pregnancy and the post partum. The preventive effect of progesterone combined with estradiol on post partum relapses is about to be tested in a large randomized and placebo-controlled European trial, the POPART'MUS study.