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While technical and medical potential offered by nanotechnologies increase, the safety assessment of engineered nanomaterials (NMs) needs to follow this pace. Inhalation is a major route of occupational and environmental exposure, and is most relevant for most of the respective safety assessment studies. Control and generation of aerosol from the test materials for this route of administration are technically demanding, and not surprisingly, there are relatively few NMs tested in toxicokinetic, short-term, and subchronic inhalation studies. These studies were in part adapted to the peculiarities of inhaled NMs, but few were also conducted according to organization for economic co-operation and development (OECD) test guidelines. Inhalation studies on the potential to develop chronic diseases, or studies to check the potential analogy to cardiovascular diseases associated with adverse health effects from ambient air pollution, are largely missing. On the way forward, appropriate inhalation studies need to be performed on a number of NMs to assess their hazards and to provide a sound database for correlation and validation of alternative in vitro methods. Moreover, these studies can potentially aid in the grouping of different NMs based on their biokinetics or biological effects. For carcinogenic and cardiovascular effects, research studies are needed to verify—or disprove—the relevance and the mechanisms by which NMs contribute to these effects. WIREs Nanomed Nanobiotechnol 2012, 4:399–413. doi: 10.1002/wnan.1173 For further resources related to this article, please visit the WIREs website.