Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, RBD without any obvious comorbid major neurological disease), is strongly associated with numerous comorbid conditions. The most prominent is that with neurodegenerative disorders, especially synuclein-mediated disorders, above all Parkinson disease (PD). Idiopathic RBD is an important risk factor for the development of synucleinopathies. Comorbidity studies suggest that iRBD is associated with a number of other potential pre-motor manifestations of synucleinopathies such as, cognitive and olfactory impairment, reduced autonomic function, neuropsychiatric manifestations and sleep complaints. Furthermore, patients with PD and RBD may have worse prognosis in terms of impaired cognitive function and overall morbidity/mortality; in dementia, the presence of RBD is strongly associated with clinical hallmarks and pathological findings of dementia with Lewy bodies. These findings underline the progressive disease process, suggesting involvement of more brain regions in patients with a more advanced disease stage. RBD is also associated with narcolepsy, and it is likely that RBD associated with narcolepsy is a distinct subtype associated with different comorbidities. RBD is also associated with antidepressant medications, autoimmune conditions, and, in rare cases, brainstem lesions.