Demyelinating disorders, characterizing by the loss of myelin integrity, present significant challenges due to their impact on neurological function and lack of effective treatments. Understanding the mechanisms underlying myelin damage is crucial for developing therapeutic strategies. Triggering receptor expressed on myeloid cells 2 (TREM2), a pivotal immune receptor predominantly found on microglial cells, plays essential roles in phagocytosis and lipid metabolism, vital processes in neuroinflammation and immune regulation. Emerging evidence indicates a close relationship between TREM2 and various aspects of myelin sheath dynamics, including maintenance, response to damage, and regeneration. This review provides a comprehensive discussion of TREM2's influence on myelin physiology and pathology, highlighting its therapeutic potential and putative mechanisms in the progression of demyelinating disorders.