Targeting progressive disease biology and promoting tissue repair is the central challenge in multiple sclerosis (MS). Stefan Bittner, MD, Johannes Gutenberg-University, Mainz, Germany, discusses current views for targeting progressive MS. Neurodegeneration in MS is linked to inflammation, even in the progressive phase. Therefore, compartmentalized adaptive and innate central nervous system (CNS) inflammation is an attractive target for novel approaches in progressive disease. Ongoing clinical trials on Bruton’s tyrosine kinase (BTK) inhibitors will provide insights into the pathological pathways of progressive MS. This interview took place at the European Academy of Neurology (EAN) 2022 Congress in Vienna, Austria.