Progressive MS represents the major unmet therapeutic need in MS, today. Our understanding od progressive MS, as a part of the full spectrum of MS, has expanded considerably. In order to better treat progressive MS we must understand how this phase of the disease develops and how to recognize the progressive course. In this teaching course we will review the definitions of progressive MS and how this is a subset of worsening MS, what the role of inflammation plays, how progression interacts with MS disease activity and how all this could lead to better therapies.