Both transition metals and heavy metals are ubiquitous in the body. There is mounting evidence to suggest that these metals play a pivotal role in the pathophysiology of neurodegenerative diseases. Consequently, sequestering these metals using chelating agents or inhibiting metal-induced oxidative stress represents an important strategy to treat or prevent neurodegenerative disease. This mini-review will provide a broad overview on the common endogenous transition and heavy metals, their biological effects and the potential of natural products to counter their deleterious effects.