Astrocytes are one of the major glial cell types that maintain homeostasis in the undamaged CNS. After injury and disease, astrocytes become reactive and prevent regeneration; however, it has also been suggested that astrocytes can become activated and promote regeneration. Thus, it is hypothesised that astrocytes have an important role in modulating CNS repair. This review will focus on the variable phenotypic state of astrocytes that range from inactive/quiescent to reactive, and relate these to their ability to influence myelination. Using myelinating cultures plated on astrocytes we propose a possible mechanism for oligodendrocyte precursor cell interaction with the axon, leading to myelination. The phenotypic status of astrocytes is an intriguing and widely discussed issue, which is critical for understanding the mechanisms involved in CNS injury and its subsequent repair.