The advent and wide use of magnetic resonance brain imaging has led to in the unexpected detection of lesions that appear typical of multiple sclerosis (MS) in otherwise asymptomatic patients. Several cohorts of patients with the "radiologically isolated syndrome (RIS)" have been studied mainly retrospectively, and a proportion of them do go on to have clinical symptoms of MS. This has led to the not infrequent clinical conundrum of whether or not to treat patients with MRI lesions suggestive of MS, given the knowledge that MS disease-modifying therapies work best when given early in the disease course. However, the decision to proactively treat patients with RIS is countered by the increasing risks associated with MS disease-modifying therapies as well as the uncertain prognostic outcome of RIS. This review will highlight what is and is not known about the long-term outcomes of RIS and present recommendations for clinicians when faced with this challenging situation.