The Restless Legs Syndrome (RLS), also known as Willis Ekbom Disease (WED), occurs commonly in many medical conditions and is affected by commonly used medications.This mosaic of multiple conditions engendering or exacerbating RLS requires altering our concepts of the underlying biology of RLS.It also impacts practical treatment considerations.This presentation will note the wide range of conditions associated with RLS and review in more depth three major ones: iron deficiency, pregnancy, and hypoxia.