The most characteristic features of the restless legs syndrome (RLS) are uncomfortable sensations in one or more usually lower limbs, associated with an urge to move the affected limbs. Those sensations vary widely in severity from merely annoying to significantly unpleasant. Periodic limb movements disorder (PLMD) can only be diagnosed when a polysomnographic recording has been performed. In the past few decades neuroimaging, neurophysiological, and pharmacological studies have contributed to the development of a variety of hypotheses on the pathogenesis of the disorder. The usually immediate and striking efficacy of treatment with dopaminergic agents, and the observation that dopamine receptor antagonism can clinically worsen RLS symptoms, indicates a central role of the dopaminergic system in RLS pathophysiology. Peripheral polyneuropathy, which, similar to RLS, often causes paresthesias and pain in the limbs and tends to worsen at night, is probably the most common differential diagnosis.