Oligodendrocyte precursor cells (OPC) are glial cells that metamorphose into myelinating oligodendrocytes during embryogenesis and early stages of post-natal life. OPCs continue to divide throughout adulthood and some eventually differentiate into oligodendrocytes in response to demyelinating lesions. There is growing evidence that OPCs are also involved in activity-driven de novo myelination of previously unmyelinated axons and myelin remodeling in adulthood. In this review, we summarize the interwoven factors and cascades that promote the activation, recruitment and differentiation of OPCs into myelinating oligodendrocytes in the adult brain based mostly on results found in the study of demyelinating diseases. The goal of the review was to draw a complete picture of the transformation of OPCs into mature oligodendrocytes to facilitate the study of this transformation in both the normal and diseased adult brain.