Migraine is very common in women of reproductive age. With peak prevalence of migraine occurring during childbearing years, many women with migraine may knowingly or unknowingly use medication during pregnancy. Although migraine tends to improve during pregnancy, many women may still experience moderate to severe disabling headache and need pharmacologic treatment for the pain, nausea, and vomiting. This article explores the physiologic changes occurring during pregnancy that can affect pharmacokinetic properties of drugs and their metabolism. Acute and preventive treatment of migraine during pregnancy and lactation is discussed, with an emphasis on safety to the fetus and nursing infant. Safety and recommended use of medication during pregnancy may be different when use is considered during breastfeeding. A goal of treatment is to balance potential risk of treatment to the fetus and nursing infant with significant relief and return to normal function of the mother.