Magnetic resonance imaging (MRI) has considerably improved the diagnosis and monitoring of multiple sclerosis (MS). Conventional MRI such as T2-weighted and gadolinium-enhanced T1-weighted sequences detect focal lesions of the white matter, damage of the blood-brain barrier, and tissue loss and inflammatory activity within lesions. However, these conventional MRI metrics lack the specificity required for characterizing the underlying pathophysiology, especially diffuse damage occurring throughout the whole central nervous system. To overcome these limitations, advanced MRI techniques have been developed to get more sensitive and specific parameters of focal and diffuse brain damage. Among these techniques, magnetization transfer imaging, diffusion MRI, functional MRI, and magnetic resonance spectroscopy are the most significant. In this article, we provide an overview of these advanced MRI techniques and their contribution to the better characterization and understanding of MS. © 2010 International Union for Pure and Applied Biophysics (IUPAB) and Springer.