The characteristic feature of multiple sclerosis (MS) pathology is the demyelinated plaque distributed throughout the central nervous system. Although MS is a primary demyelinating disease, acute axonal injury is common in actively demyelinating MS lesions and it is considered one of the major determinants of neurological deficit. Magnetic resonance imaging (MRI) has had a dramatic impact on MS in both the clinical practice and basic science settings. Techniques such as T2-weighted and gadolinium-enhanced T1-weighted MRI are very sensitive in detecting lesions and, thus, increase the level of certainty of MS diagnosis. Conventional MRI has also improved our understanding of the pathogenesis of the disease and has provided objective and reliable measures to monitor the effect of experimental treatments in clinical trials. However, conventional MRI does not provide specific information on the heterogeneous pathologic substrate of MS lesions. Advanced MRI techniques, such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy, offer the unprecedented ability to observe and quantify pathological changes in lesions and normal-appearing brain tissue over time. The present review will discuss the major contributions of conventional MRI and quantitative MRI techniques to understand how individual MS lesions evolve.