Multiple sclerosis (MS) involves ongoing accumulating CNS damage. Precisely which environmental factors trigger onset and progression of the disease are not known. However, clinical trials indicate benefits from early use of disease-modifying therapies (DMTs). All the completed clinically isolated syndrome trials (CHAMPS, ETOMS, BENEFIT, PRECISE) reported significant suppression of subsequent relapse and MRI lesion formation from use of DMT at the first relapse. This article reviews data on early treatment. Such an approach requires the ability to recognize clinically isolated syndrome features that indicate a diagnosis of MS.