The increasing application of nanotechnology in various industrial, environmental, and human settings raises questions surrounding the potential adverse effects induced by nanosized materials to human health, including the possible neurotoxic and neuroinflammatory properties of those substances and their capability to induce neurodegeneration. In this review, a panel of metal oxide nanoparticles (NPs), namely titanium dioxide, silicon dioxide, zinc oxide, copper oxide, iron NPs, and carbon nanotubes have been focused. An overview has been provided of the in vitro and in vivo evidence of adverse effects to the central nervous system. Research indicated that these nanomaterials (NMs) not only reach the brain, but also can cause a certain degree of brain tissue damage, including cytotoxicity, genotoxicity, induction of oxidative stress, and inflammation, all potentially involved in the onset and progression of neurodegeneration. Surface chemistry of the NMs may play an important role in their localization and subsequent effects on the brain of rodents. In addition, NM shape differences may induce varying degrees of neurotoxicity. However, one of the potential biomedical applications of NMs is nanodevices for early diagnostic and novel therapeutic approaches to counteract age related diseases. In this context, engineered NMs were promising vehicles to carry diagnostic and therapeutic compounds across the blood–brain barrier, thereby representing very timely and attractive theranostic tools in neurodegenerative diseases. Therefore, a careful assessment of the risk–benefit ratio must be taken into consideration in using nanosized materials. Environ. Mol. Mutagen. 56:149–170, 2015. © 2015 Wiley Periodicals, Inc.