Restless legs syndrome (RLS) is a common and often underestimated neurological disorder, with a prevalence ranging from approximately 2.5% to 10% in Western industrialized countries. The aim of the present study was to summarize the research findings on the human and economic costs associated with RLS in populations without any co-morbidities or potentially confounding health conditions. A further objective was to identify studies on the cost effectiveness of RLS treatments. A systematic literature search was performed. Two researchers independently assessed the relevance of each publication. Studies published before August 2008 were included if they assessed quality of life in patients suffering from RLS, determined total or patient-related costs attributable to RLS, and/or evaluated the cost effectiveness of treatment options for RLS. A total of 725 references were identified, including 100 full-text articles. Fifteen of these publications met all of the selection criteria and were included in the present review. Seven abstracts that focused on the economic burden of RLS and/or the cost effectiveness of different treatment strategies in RLS patients were also included. RLS was associated, in the included studies, with reductions in quality of life similar to those seen in patients with other chronic conditions. The cost-of-illness studies were heterogeneous but indicated that RLS was associated with a substantial economic burden, resulting in high direct and indirect costs to society. Although effective and cost-effective treatments appear to be available, further research is warranted, especially regarding the economic burden of RLS and the cost effectiveness of available treatment options.