Multiple sclerosis (MS) features extensive neurodegenerative pathology, in addition to the well-known neuro-inflammatory lesions. Recent breakthroughs highlight the importance of slow physical and cognitive progression in MS, which can continue despite effective slowing of lesion formation through high efficacy treatment. These types of progression seem driven to a large extent by neurodegenerative changes in MS, highlighting the need for more research to achieve clinical implementation with clear cut-off scores and monitoring strategies. This mini review outlines possible mechanisms underlying neurodegeneration, how to measure these processes on MRI and how we can move towards implementation.