A proper clinical evaluation of patients with Multiple Sclerosis (MS) is of great importance to detect MS progression. It provides important data for physicians on their daily practice as well as with scientific purpose, especially useful with the development of newer therapeutic options in MS. Clinical outcome measures (COMs) are instruments that enable a standardized characterization of the patient's clinical disease status. A proper COM should have - among other psychometric characteristics - a good validity, reliability and responsiveness. For MS disability, the Expanded Disability Status Scale (EDSS) is currently the most frequently used scale. However, different less known COMs are also available and could be implemented on clinical practice. We review the most frequently used COMs of MS progression including their operationalization and statistical considerations, as well as newer composite COMs and digital tools on development. We focus on their responsiveness or capacity to detect clinically relevant changes to identify progression or transition to progressive forms of the disease, as well as therapeutic response.