Restless legs syndrome (RLS) is characterized by a compelling, often insatiable, need to move the legs, accompanied by unpleasant sensations located mainly in the ankles and calves. Because symptoms are brought on by inactivity, distress intrudes upon everyday, sedentary activities such as plane travel, car rides, and attending school, meetings, or the theatre. Symptoms show a diurnal preference for the evening and night, so disruption of sleep onset or maintenance is particularly common. RLS is associated with both lower ratings of quality of life and higher rates of cardiovascular disease. Four common genetic loci associating to RLS have recently been identified, but the molecular pathways by which they increase risk for RLS have yet to be determined. Both sensory (RLS) and motor (periodic limb movements of sleep) symptoms are responsive to dopaminergic medications, yet clear delineation of dopaminergic pathology has not emerged. Brain iron is reduced in many, but not all, patients with RLS. First-line treatment for RLS includes agents acting at D(2) and D(3) dopamine receptors.