C o m m e n t a R YR estless legs syndrome (RLS), also known as Willis-Ekbom disease, is now generally appreciated in the medical literature as common and complex. Over 50 prevalence studies, most published since 2005, have been crucial in defi ning many important clinical aspects. In this issue of JCSM is one of the fi rst general population-based incidence studies of RLS. 1 How are incidence studies different, and how might they further clinical knowledge?First, let us review the "Top Five" agreed upon fi ndings from prevalence studies of RLS. 2 Number 5: Prevalence in females is about twice as high as in males, beginning in the late teens or 20s. Number 4: Association with other conditions. Individuals with RLS are at least twice as likely to have scores indicating a depressive or anxiety disorder. This has major clinical implications in that common treatments for these disorders can worsen RLS, 3 and because ongoing sleep disturbance is a known risk factor for the onset and persistence of depressive disorders, as well as for suicidality. Interestingly, emerging evidence indicates at least twice the risk of cardiovascular disease in RLS. Less agreement has been found regarding increased comorbidity with numerous other disorders, including hypertension, diabetes, and obesity. Number 3: Quality of life (QOL) impairments are signifi cant in moderate-to-severe RLS, comparable to diabetes and congestive heart failure. 4 These include lower physical and mental health scores, with disturbed sleep very common by both subjective and objective measures. Number 2: There is a wide spectrum of frequency/severity. Of those meeting the four essential IRLSSG criteria, application of frequency at least 1x/week represents 60% of the RLS population; at least 2x/week is about 50%; and daily is about 20%. Clinically signifi cant RLS-RLS associated with higher morbidity and where treatment should be considered-can be defi ned by frequency/severity measures. Occurrence at least 1-2x/week, typically with moderate to severe distress, is the most common defi nition in the epidemiologic studies that show impairment.Number 1: Consideration of differential diagnosis is very important. Exclusion of "mimics" of RLS, such as leg cramps, positional discomfort, arthritis, and leg edema, leads to specifi city of diagnosis, 5 and prevalence rates of 1.9% to 4.6% for moderate-to-severe RLS in European and North American studies. 2 Without differential diagnosis prevalence estimates are about 1.25 to 2 times higher. Importantly, the 2012 revision of the International RLS Study Group (IRLSSG) diagnostic criteria will include differential diagnosis as a 5 th essential criterion, as is also planned for the International Classifi cation of Sleep Disorders (ICSD-3) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013.Incidence rate is an estimate of the number of new cases in a population over a given time period, as compared to prevalence, which estimates the total number of cases in a population at a given time. Incidence pr...