Multiple sclerosis (MS) is a chronic immune-mediated inlfammatory-demyelinating disorder of the central nervous system, with a strong neurodegenerative component. The question whether neurodegeneration in MS is independent or related to neuroinlfammation has been long debated, but not yet fully clariifed. Furthermore, little is still known on how neuroinlfammation and neurodegeneration in MS are related to potential regenerative processes. In this perspective, we brielfy discuss main clinical, pathological and ex-perimental evidence on the relationship between neuroinlfammation and neurodegeneration in MS, and on their connection with regeneration. We discuss that these processes in MS might represent intercorrelated manifestations of the immune response, especially of the innate immunity.