Several diseases may cause non-specific MR signal abnormalities of the bilateral basal ganglia and thalami. As such, diagnosis of the underlying etiology may be difficult to achieve at imaging. In this review, we will present interpretative guidelines based on clinical data (mode of presentation, previous history, clinical symptoms, and evolution) and imaging data (type of signal abnormalities, location of lesions, and associated abnormalities). The main categories of diseases causing MR signal abnormalities of the bilateral basal ganglia and thalami in adults are reviewed: toxic, metabolic, vascular, tumoral, infectious and inflammatory diseases.