Myelin regenerates spontaneously after demyelination. This process is called "remyelination". For remyelination to be successful, cellular debris from tissue injury must be removed and new oligodendrocytes must be available to replace myelin. These events require a sequence of well-controlled signals that regulate inflammation and endogenous neural stem/precursor cell mobilization and differentiation to restore form and function to the CNS. The major players of remyelination are (1) oligodendrocyte precursor cells (OPCs), which are widely distributed neural progenitors in the adult CNS that are able to differentiate into oligodendrocytes, (2) microglia, which are the widely distributed immune-surveillance cells in the adult CNS that are needed for debris clearance and regulation of inflammation, (3) axons, which provide the signal(s) and membrane surface for oligodendrocytes to interact with and synthesize myelin, and (4) astrocytes, which form a structural barrier (scar) around the lesion and influence inflammation. After CNS demyelination, remyelination is achieved by the coordinated expression of regenerative signals at the lesion that promotes inflammation and oligodendrocyte precursor proliferation/migration, followed by those that decrease inflammation and induce oligodendrocyte differentiation and myelin synthesis. We have identified many of these signals from a microarray analysis of CNS remyelination (Huang et al., 2011), and are currently investigating their roles in remyelination.