The initial phases of the clinical course of relapsing−remitting multiple sclerosis (MS) are characterized by a mainly inflammatory pathology which gives way to a largely neurodegenerative process as the disease evolves. As all currently available disease-modifying therapies aim to control inflammation, the window of opportunity for use is early in the disease course, specifically at the time of a clinically isolated syndrome suggestive of MS or in the early stages of relapsing−remitting MS. Approximately 30% of patients treated with first-line immunomodulators (interferon-β or glatiramer acetate) show a suboptimal response during the first 1–2 years and require a switch to an alternative therapy. It is recommended not to wait too long to switch in order to prevent disease progression. Patients with a poor prognosis in particular may require a timely switch to a second-line agent. Regular monitoring of disease and therapy in patients with MS is essential. In the first year after diagnosis, clinical evaluations (neurological status, symptomatic assessment, patient well-being) should be performed at baseline, 3, 6 and 12 months, and then every 6 months thereafter. Brain magnetic resonance imaging (MRI) should be performed every 6 months in the first year of treatment, and at least once yearly thereafter. A spinal cord MRI should be performed once yearly in patients presenting spinal symptoms.