This update on restless legs syndrome (RLS) focuses on its pathophysiology, genetics, health impact, and treatment. Although symptoms are exquisitely responsive to dopaminergics, clear delineation of dopaminergic pathology has not emerged. Rather, heuristic models of alterations in spinal sensorimotor circuits and central nervous system iron deficiency are gaining more attention. Genome-wide association studies have recently identified polymorphisms in three genes with no obvious relationship to dopamine that account for 70% of the population risk for RLS. A single variant in the BTBD9 gene on chromosome 6 contributes to 50% of the population risk. Although the functions of BTBD9 remain uncertain, its biological plausibility is evidenced by its dose-dependent relationship to periodic limb movements of sleep, decrements in iron stores, and ethnic differences in RLS prevalence. RLS is also implicated in cardiovascular morbidity. Despite these advances in our knowledge, there remain unanswered questions about the pathophysiology of RLS as well as its genetics, health-related significance, and treatment.