Restless legs syndrome (RLS) affects about 20% of all pregnant women. RLS symptoms are usually moderate to severe in intensity during pregnancy and can result in insomnia, depression, and other adverse outcomes. Although iron deficiency has been implicated as a potential etiological factor, other mechanisms can also play a role. Nonpharmacologic methods are the primary recommended form of treatment for RLS in pregnancy and lactation. Iron supplementation may be considered when the serum ferritin is low; however, several patients are unable to tolerate iron or have severe symptoms despite oral iron replacement. Here, we describe a case of severe RLS in pregnancy and illustrate the dilemmas in diagnosis and management. We review the literature on the prevalence, diagnosis, course, possible underlying pathophysiologic mechanisms and complications of RLS in pregnancy. We describe current best evidence on the efficacy, and safety of nonpharmacologic therapies, oral and intravenous iron supplementation, as well as other medication treatments for RLS in pregnancy and lactation. We highlight gaps in the literature and provide a practical guide for the clinical management of RLS in pregnancy and during breastfeeding.