The restless legs syndrome (RLS) is a common sensorimotor disorder characterizedby an irresistible urge to move the legs with or without accompanying sensory discomfort that worsens with inactivity, especially during night and temporarily improves with activity.RLS encompasses an idiopathic form of genetic or unknown origin and symptomatic forms secondary to other medical conditions.Symptomatic forms are associated with iron deficiency, uremia, pregnancy, polyneuropathy, rheumatoid arthritis, and so on. CNS dopaminergic systems are strongly implicated in RLS that are closely linked to CNS iron homeostasis. Evidences showing the efficacy of dopaminergic drugs, the augmented circadian dopaminergic variation, and the CNS iron dysregulation support this hypothesis. Iron deficiency, uremia, and pregnancy precipitate the disturbances in CNS iron metabolism. Iron dysregulation is also documented in idiopathic form. Besides defective dopaminergic system that is closely related with iron metabolism, genetic factors play a role in early-onset individualwith a positive family history.