After the advent of immunomodulatory treatment in Multiple Sclerosis and after several options for early treatment have become available, the early identification of patients non responder has become a very important issue. Therefore, methods are needed for the detection of disease activity and, particularly in more advanced phases of the disease, of disease progression. Neurophysiological methods, mainly evoked potentials (EPs), are widely used in the functional assessment of sensory and motor pathways. Their usefulness in the assessment of disease activity is limited by the fact that, although they can also reveal clinically silent lesions, EPs abnormalities are present only if their corresponding pathway is involved. With this respect, EPs have been extensively replaced by magnetic resonance imaging (MRI), with the exception of optic nerve in which the sensitivity of EPs and MRI is similar. Nevertheless, EPs can be useful for the assessment of disease progression, since their abnormalities have been demonstrated to be more strictly related to disability than MRI lesion burden. With this perspective, EPs can still be useful in the identification of non responder by providing the clinician with objective functional assessment of eloquent pathways in patients with ambiguous new symptoms, for the confirmation of a dubious relapse, and by providing a method for detecting worsening of nervous conduction for the confirmation of disease progression.