Introduction: Neurologists are frequently consulted for patients who have white matter lesions discovered incidentally on their brain MRI, performed for reasons other than suspecting a demyelinating disease. The referring physician will question if the person has multiple sclerosis (MS). If the MRI is typical for MS but there are no clinical symptoms or signs suggestive of a demyelinating disorder, patients are diagnosed as having a Radiologically Isolated Syndrome (RIS).Areas covered: This is a timely review on RIS with a focus on treatment considerations.Expert commentary: Multiple studies have tried to identify common predictive factors for conversion of RIS to clinical MS, the strongest thus far being an asymptomatic cervical spinal cord lesion. Treatment of RIS is highly controversial, but early treatment in carefully selected patients might improve long term outcome.