Failure of regeneration capacity limits the restoration of nervous system functionality in demyelinating diseases such as multiple sclerosis. Yet, the responsible mechanisms are only partially understood. I will present data supporting a key role for lipid metabolisms (that is, lipid droplet biogenesis and cholesterol efflux) in phagocytes for regeneration of myelin. Stimulation of the lipid sensing Triggering receptor expressed on myeloid cells or nuclear liver X receptor are possible therapeutic strategies of how to enhance the capacity to regenerate lesioned tissue.