Descriptors of multiple sclerosis are currently based on a combination of clinical and MRI features, and include clinically isolated syndrome, relapsing-remitting, secondary and primary progressive subtypes. Accumulating evidence suggests that the clinical course of MS is better considered as a continuum, with contributions from concurrent pathophysiological processes that vary across individuals and over time. In this episode, MS Journal Editor in Chief Alan Thompson talks with neurologists Marcello Moccia of the Multiple Sclerosis Unit of the University of Naples Federico II and Angela Vidal of Centre d'Esclerosi Multiple de Catalunya on the new understanding of the key mechanisms underlying progression and the availability of neuroimaging and humoral biomarkers and their implications for clinical care and treatment.