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With the rapid development of new nanomaterials, it was recognized early that together with their beneficial properties, nanomaterials may pose a risk to human health and the environment. Evidence has accumulated over the last twenty years in support of oxidative stress as a broad mechanistic concept to explain the interaction of engineered nanoparticles with biological substances. As oxidative stress as a physiological response was recognized in redox biology, its wide-ranging use in nanotoxicology has exposed new challenges and limitations. In this commentary, we review certain oxidative stress concepts and their relevance to nanotoxicology.