The field of nanotechnology currently is undergoing a dramatic expansion in material science research and development. Most of the research efforts have been focused on applications; the implications (i.e., health and environmental effects) research has lagged behind. The success of nanotechnology will require assurances that the products being developed are safe from an environmental, health, and safety (EHS) standpoint. In this regard, it has been previously reported in pulmonary toxicity studies that lung exposures to ultrafine or nanoparticles (defined herein as particle size <100 nm in one dimension) produce enhanced adverse inflammatory responses when compared to larger particles of similar composition. Surface properties (particularly particle surface area) and free radical generation, resulting from the interactions of particles with cells may play important roles in nanoparticle toxicity. This brief review identifies some of the key factors for studying EHS risks and hazard effects related to nanoparticle exposures. Health and environmental risk evaluations are products of hazard and exposure assessments. The key factors for discussion herein include the importance of particle characterization studies; development of a nanomaterial risk framework; as well as corresponding hypothesis-driven, mechanistically-oriented investigations, concomitant with base set hazard studies which clearly demonstrate that particle size is only a single (and perhaps minor) factor in influencing the safety of nanomaterials.