This monograph is an up-to-date report of the most recent advances in the research on primary progressive multiple sclerosis (PPMS) - a variant of MS - and of the considerable progress made in understanding it. The reviews demonstrate that the advances in understanding the natural history, pathophysiology, pathogenesis and pathology of PPMS are being extended by ongoing studies of the MS plaque and normal appearing white matter using magnetic resonance imaging and spectroscopic techniques. This confluence of thought provides insight into possible disease mechanisms.