BACKGROUND: Restless legs syndrome (RLS) is a movement disorder treated with dopamine agonists. RLS is often diagnosed as a comorbid condition with psychiatric disorders, which are treated with dopamine antagonists or antidepressants resulting in onset or exacerbation of RLS symptoms. OBJECTIVES: The objectives of this article are to provide a review of the literature to (a) describe the comorbidity of psychiatric disorders associated with RLS, (b) identify the treatment of psychiatric disorders that cause or exacerbate symptoms of RLS, and (c) provide clinical recommendations for psychiatric health care providers. DESIGN: A review of the literature of English articles included the databases of Medline, Pubmed, PsychINFO, and CINAHL for “Restless Legs Syndrome” with major psychiatric disorders including mood disorders (depression and bipolar), schizophrenia, and anxiety disorders (anxiety, panic disorder, obsessive compulsive disorder). The PRISMA guidelines were used to improve the reporting of the review of the literature. RESULTS: There were 61 articles that met the inclusion and exclusion criteria identified for the review of the literature, including RLS with mood disorders (n = 36), schizophrenia (n = 9), and anxiety disorders (n = 16). CONCLUSIONS: Clinical trials are lacking on the best treatment for persons with RLS and psychiatric disorders; the most rigorous research found in the literature related to depression and anxiety. Studies lack evidence to document the best practice for persons with RLS and comorbid psychiatric disorders. Psychiatric health care providers should be aware of RLS, which is influenced by psychiatric medications.