MR imaging is an integral part of multiple sclerosis (MS) clinical trials. It provides the primary efficacy outcome of preliminary proof-of-concept studies and important corroborating data as secondary and exploratory outcomes in pivotal trials. At all stages of drug development, MR imaging provides important information on the kinetics and magnitude of treatment effect and insight into potential mechanisms of action. Attention to issues in scan acquisition, quantitative image processing, and statistical analysis is critical to generate high-quality data. Although it is unlikely that one single outcome measure can capture all aspects of the MS disease process, there is potential for MR imaging outcomes to evaluate inflammatory and degenerative components within clinical trials.