Abstract: Redox active metals such as iron, copper, zinc, and manganese play important roles in promoting a variety of biochemical reactions essential for cellular function. This is made possible by the ability of these metals to accept and donate electrons. Iron in the form of iron-sulfur clusters and heme plays a key role in adenosine triphosphate generation in mitochondria as well as numerous other enzymatic reactions. On the other hand, disruption in the normal homeostatic levels of these metals, either excess or reduction, results in damage to cells and to tissue pathology. Excess copper accumulation in the central nervous system (CNS) in Wilson’s disease results in damage to the basal ganglia, and excess iron deposition in the CNS in aceruloplasminemia results in damage to various regions of the brain and retina. Such damage is thought to be induced by free radicals generated via Fenton chemistry. Here, we focus on our recent work that revealed a role for ferroptosis, a form of iron-mediated cell death, in cuprizone-induced oligodendrocyte loss and demyelination (Jhelum et al., 2020). Cuprizone is a copper chelator that induces demyelination in experimental animals and is widely used to study demyelination and remyelination in the CNS (Zhan et al., 2020), often in the context of multiple sclerosis (MS), the prototypical demyelination disease in humans. Another key finding in this work is the potential role of ferritinophagy in ferroptosis, i.e., the release of iron from cytosolic ferritin (Dixon et al., 2012; Mancias et al., 2014). This work also shows the link between copper and iron metabolism, in which chelating copper leads to dysregulation of iron metabolism. Importantly, ferroptosis may also play a role in other neurological conditions and deserves further study.