With the passage of the National Nanoscale Initiative in 2001 there has been increasing attention and funding given to nanomaterial research. This has led to a number of new materials developed at the nanoscale (< 100 nm) level, which often possess chemical and physical properties distinct from those of their bulk materials. These unique qualities are proving to be quite useful in a number of new applications. For example, biological applications in imaging, treatment, and drug delivery are particularly promising as well as the increasing engineering potential of nanocircuitry and materials science. As the number of applications increases however, so too does the potential for human exposure to nanomaterials through a number of routes: dermal, ingestion, inhalation, and even injection. Interestingly some of the properties of these nanomaterials that make them useful in these emerging technologies are the same properties that can increase their toxic potential. This is leading to an emerging discipline – nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Nanotoxicology research will not only provide information for risk assessment of nanomaterials based on data for hazard identification, dose response relationships and biokinetics, but will also help to further advance the field of nanoresearch by providing information to alter undesirable nanomaterials properties. Although nanotoxicology is in its infancy, there are some preliminary studies with newly developed materials that provide some insight into potential effects, which when coupled with older studies provides some insight on how these nanomaterials impact the biological system. This presentation summarizes results of studies with nanosized particles with a focus on the respiratory system and skin as portals of entry. The ability of particles to translocate from their site of entry, their ability to elicit biological responses, and their presumed mechanisms of action will be highlighted. This will be an attempt to illustrate how pervasive these materials can be, which may or may not be detrimental. With proper toxicological assessment this potential may be harnessed leading to breakthroughs at the nanotechnology – biology interface.