Myelin, made by oligodendrocytes in the central nervous system, is essential to nervous system formation and function, well known for its role in facilitating rapid nerve impulse conduction. Damage to or disruption to myelin is increasingly evident in numerous diseases that span the life course, from neurodevelopmental disorders, neuropsychiatric conditions, through to age-related neurodegenerative diseases. Despite the importance of myelin, we have much to learn about how it is formed on certain axons at certain times of life, how it is dynamically regulated within specific circuits and how this affects their function, and how it responds to different damaging insults across diverse injuries and disease. In this talk I will present our work using zebrafish as a discovery model, which has revealed unexpected plasticity in how myelin sheaths are wrapped around axons, how myelin responds to neuronal activity, and how mature myelin respond to damage. I will show how discoveries in zebrafish led to identification of conserved mechanisms of myelin plasticity in the mammalian and human nervous system that may have important implications for the treatment of disease.