Restless legs syndrome (RLS) is a complex sensorimotor disorder characterized by disturbances in key neurochemical pathways, including dopaminergic, glutamatergic, and adenosinergic systems. This review provides an overview of the current knowledge on RLS, including its clinical features and diagnosis, pathophysiology, and treatment (non-pharmacological and pharmacological). We examine the association between RLS and neurological disorders, genetic predispositions, and brain iron deficiency. Emerging therapies targeting glutamate and adenosine receptors, alongside established dopamine agonists and α2δ ligands, offer promising avenues for treatment.