The symptoms of restless legs syndrome (RLS) can be managed effectively by treatment. The pathophysiology of primary RLS is only partly understood; however, a strong association with brain iron deficiency, which possibly impairs dopaminergic function, has been identified. Dopamine agonists are the mainstay of RLS treatment, but other therapies, including gabapentin, benzodiazepines, and low-potency opioids, are also commonly employed. Recent evidence-based guidelines recommend dopamine agonists or alpha-2-delta ligands as the first-line treatment for RLS depending on patients' clinical background, comorbidity, and severity of the symptoms. In this review, we focus on the pathophysiology, comorbidity, differential diagnosis, and novel treatment approaches of RLS.