The cause of multiple sclerosis (MS) remains unknown despite decades of intense research. The major research disciplines that have been brought to bear on this question include genetics, epidemiology, neuropathology, immunology, and virology. Recent advances in the understanding of the inflammatory characteristics of the MS lesion may herald the development of specific and effective treatments. The goal of this research is to improve our management of a disease that remains the major cause of neurologic disability among young adults in North America and Europe.