Magnetic resonance imaging (MRI) is the most important paraclinical measure for assessing and monitoring the pathologic changes implicated in the onset and progression of multiple sclerosis (MS). Conventional MRI sequences, such as T1-weighted gadolinium (Gd)-enhanced and spin-echo T2-weighted imaging, provide an incomplete picture of the degree of inflammation and underlying neurodegenerative changes in this disease. Two- and three-dimensional fluid-attenuated inversion recovery and double-inversion recovery sequences allow better identification of cortical, periventricular, and infratentorial lesions. High field strength MRI has the potential to detect more cortical and deep gray matter lesions, but the detection of subpial cortical lesions in MS remains challenging. Unenhanced T1-weighted imaging can reveal hypointense black holes, a measure of chronic neurodegeneration. Magnetization transfer imaging (MTI) is increasingly used to characterize the evolution of MS lesions and normally appearing brain tissue, and evidence suggests that the dynamics of magnetization transfer changes correlate with the extent of demyelination and remyelination. Magnetic resonance spectroscopy, which provides details on tissue biochemistry, metabolism, and function, also has the capacity to reveal neuroprotective mechanisms. By measuring the motion of water, diffusion imaging can provide information about the orientation, size, and geometry of tissue damage in white and gray matters. Iron imaging-related techniques such as susceptibility-weighted imaging (SWI) have enormous potential for identifying iron-related pathology in MS. These advanced non-conventional MRI techniques relate better to clinical impairment, disease progression, and accumulation of disability and have the potential to detect neuroprotective effects of treatment.