For women with multiple sclerosis (MS) who become pregnant, the risks and benefits of ongoing therapy for the health of both the mother and the fetus must be carefully considered. Based on a literature review and our MS center's standard practices, we provide guidance to aid clinical decision making in the absence of clear evidence-based clinical practice guidelines. Women seeking to achieve pregnancy should generally discontinue disease-modifying therapy use prior to attempting conception. For example, the immunosuppressant mitoxantrone is teratogenic and should be prescribed only with the assurance of effective contraception. Conception should be discouraged for patients on fingolimod, because of the limited information available on human pregnancy outcomes. Current evidence, including data from pregnancy registries for glatiramer acetate (GA), interferon beta-1a (IFNβ-1a), and natalizumab, has not shown specific patterns of malformations suggesting teratogenicity. Pregnancy registry data have not been published for IFNβ-1b. During breastfeeding, intravenous immunoglobulin and corticosteroids are generally safe and may be associated with a reduction in postpartum relapses; however, a washout period is recommended between corticosteroid administration and the resumption of breastfeeding. Clinical data on the use of IFNβ, GA, and natalizumab during lactation are limited. Mitoxantrone is contraindicated during breastfeeding, and fingolimod should be avoided in nursing mothers, because of a lack of data.