The McDonald diagnostic criteria have allowed the formal diagnosis of multiple sclerosis in patients presenting with clinically isolated syndromes to be brought forward. Evidence from research suggests that many patients with clinically isolated syndromes or early multiple sclerosis should be treated with disease-modifying drugs at an early stage, since disease experience during the first few years are likely to have significant impact on the long-term evolution of the disease. Histopathological studies have demonstrated the presence of axonal transection in patients with less than five years of disease duration, and especially during the first twelve months. Natural history studies have shown that the number of relapses occurring during the first few years of the disease is related to the time to accrued disability. Moreover, longitudinal studies on patients with clinically isolated syndromes have shown that the presence of even a very small number of baseline MRI lesions is associated with an increased risk of developing clinically definite multiple sclerosis and, more importantly, that the increase in volume of the lesions seen in the first five years correlates with the degree of disability in the longer term. For example, long-term follow-up of a large cohort of patients presenting with a clinically isolated syndrome in Barcelona has shown that the number of Barkhof criteria fulfilled at baseline was correlated with the risk of relapse, EDSS disability scores at five years and the risk of reaching given EDSS disability thresholds. Three randomised clinical trials in patients with a clinically isolated syndrome and abnormal brain MRI have shown significant benefit of initiating early therapy with beta-interferons, and a similar study is underway with glatiramer acetate. It is concluded that choosing the right time to introduce treatment is critically important for outcome and the earlier treatment is initiated, the better the outcome.