Nanomaterials exhibit novel, size-dependent properties that enable new applications ranging from molecular electronics to energy production. An early concern, expressed nearly 20 years ago, was that the novel properties associated with size might also translate into previously un-recognized modes of toxicity to organisms and ecosystems that might be generalized to the entire class of “nanomaterials.” Exposure to nanomaterials may arise during nanomaterial fabrication, handling of nanomaterials in subsequent processing to create derivative products, product usage, and as the result of post-usage or waste disposal practices. Hazards suggested for nanomaterials included that of the Trojan horse effect (conventional contaminants carried by nano-scale materials), alterations in protein configuration, oxidative stress, redox reactions, and others. The quantities of nanomaterials produced per year are large and the number of products incorporating nanomaterials has grown rapidly. However, apart from work-place exposures, these quantities are miniscule compared with exposures to natural and incidental nano-scale materials. While still controversial, research over the last 20 years has not yielded evidence for a uniquely nano-based pathway for toxicity. Individual types nanomaterials have been shown to exhibit toxicity, such as in the case of heavy-metal derived nanoparticles. Nanoscale formulations of these materials, previously known to be toxic in their bulk form, may yield dose-response curves that differ from their bulk counterparts. However, evidence is lacking for nano-based phenomena that produce toxicity in a general sense that would merit broad-brush regulation of nano-scale materials. This presentation briefly reviews the evidence for nanomaterial toxicity, considers the relative exposures to nano-scale materials and presents some the attributes of nanomaterial behavior in natural systems that have been described over the last 20 years.