Despite years of investigation, it is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders. Also, it is not clear whether iron accumulation in the brain is an initial event that causes neuronal death or is a consequence of the disease process. Here, we propose that iron and iron-induced oxidative stress constitute a common mechanism that is involved in the development of neurodegeneration. Also, we suggest that, at least in some neurodegenerative disorders, brain iron misregulation is an initial cause of neuronal death and that this misregulation might be the result of either genetic or non-genetic factors.