The term prodrome often refers to symptoms indicating disease onset before diagnostically specific signs or symptoms emerge. Data from several recent studies have pointed toward a possible prodromal phase of multiple sclerosis (MS).1 These studies have retrospectively identified increased prevalence of symptoms, diagnoses, and health care use in patients years before a new diagnosis of MS.1 An increased prevalence of fatigue, depression, anxiety, headache, sleep disturbances, pain, musculoskeletal disorders, gastrointestinal disorders, and genitourinary disorders, even when patients with diagnoses compatible with concurrent neurologic syndromes were excluded, appeared to precede diagnosis of MS. These data suggest a potential window of opportunity to affect disease trajectory if prodromal symptoms attributable MS could be recognized at the time of onset, or through screening efforts, because earlier treatment is associated with better clinical outcomes. An important limitation of earlier studies was the inclusion of cases reported since the 1980s, when MRI was not available to facilitate earlier diagnosis. The unusually older median age at diagnosis in these investigations indicates that many MS cases escaped early recognition and were diagnosed years later and that reported prodromal symptoms may not have preceded neurologic symptoms diagnostically specific for MS.