Heme is essential for the survival of most organisms, despite the fact of being potentially toxic. This dual effect is due to the ability of the iron (Fe) atom contained within the protoporphyrin ring of the heme molecule to participate in redox reactions and exchange electrons with a variety of substrates. Therefore, the pro-oxidant reactivity of heme needs to be kept under control, an effect achieved by its incorporation into the heme pockets of hemoproteins, i.e. proteins required to exert vital biological functions in which heme acts as prosthetic group. The release of heme from hemoproteins and the participation of Fe in the Fenton reaction lead to the generation of unfettered oxidative stress and programmed cell death. Although further investigations would be required to elucidate the regulation of heme in the brain, this molecule appears to be critically involved in the pathogenesis of different neurodegenerative diseases, as heme accumulation or deficiency is associated with impaired brain activity and neuronal death. Thus, the aim of this review is to provide an overview on the importance of heme in the brain and the pathophysiologic consequences associated with its accumulation.