Since its introduction in the 1980s, magnetic resonance imaging (MRI) has become an essential tool in supporting the diagnosis, monitoring, and evaluation of therapeutic response in multiple sclerosis (MS). Although MS is mostly a clinical diagnosis, MRI has the ability to sensitively and noninvasively demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord in the axial, sagittal, and coronal planes that are characteristic of MS (Figure 6.1). In this chapter, we discuss basic MRI sequencing techniques and provide examples of common radiographic findings in MS and MS mimics. Note that the list of alternative diagnoses presented in this chapter is not all-inclusive.