Several studies demonstrated that 60% of restless legs syndrome (RLS) patients have a positive family history and it has been suggested that RLS is a highly hereditary trait. To date, several loci have been mapped but no gene has been identified yet. Phenocopies and possible nonpenetrants made it difficult to detect a common segregating haplotype within the families. Defining the exact candidate region is hampered by possible intrafamilial, allelic, and nonallelic heterogeneity. One important prerequisite for future successful genetic studies in RLS is the availability of large and thoroughly phenotyped patients and family samples for linkage as well as association studies.