Newer outcome-based assessment methods have been developed that complement and improve upon the ability of historical clinical and magnetic resonance imaging (MRI) outcome measures to measure multiple sclerosis (MS) disease activity, patient functionality, treatment efficacy, and the risk of MS disease progression. These newer MS outcome assessments include instruments to evaluate cognitive function and patient quality of life; enhanced measures of disability, such as the Multiple Sclerosis Functional Composite instrument; and newer MRI measures of MS disease activity and neuronal changes, such as permanent T₁ hypointensities and central nervous system atrophy. When utilized in conjunction with standard MS outcome measures, these newer MS outcomes provide a more comprehensive picture of disease status and course and hold promise as tools for use in the development and testing of future MS therapies. The well-established first-line MS therapy intramuscular interferon beta-1a, which has been evaluated using a broad range of assessment methods, was used as a reference MS disease-modifying therapy to provide specific examples of studies utilizing newer evaluation methods. Utilization of evolving disease and assessment measures for patients with MS should improve MS patient diagnosis, treatment decisions, and monitoring of therapy.