Restless legs syndrome is a disorder of the nervous system that often begins in childhood, is chronic, and typically progressive, and more often affects women and those of Northern European descent in which patients experience a compelling urge to move their legs that worsens with inactivity, is relieved by movement or counter stimuli, and that is most aggravating in the evening and at night. The seminal description of RLS in 1945 by Ekbom noted additional key features: 1) a high prevalence (≥ 5%); 2) some patients who perceive RLS sensations as pain; 3) a proclivity to affect pregnant women; 4) heritability; and 5) favorable responses to iron supplementation. A second advance came with recognition that periodic leg movements in sleep (PLMs) are present nearly all RLS subjects. A third major advance has come with demonstration that drugs acting at brain dopamine receptors, opiates, and derivatives of gabapentin relieve both the sensory (RLS), and motor (PLMs) symptoms. A fourth advance has been demonstration of reductions in brain iron in some RLS cases. The fifth seminal advance has been identification that multiple genes account for the majority of one’s risk for RLS and PLMs.