The large-scale production and consumer exposure to a variety of nanotechnology innovations has stirred interest concerning the health consequences of human exposure to nanomaterials. In order to investigate these questions, in vitro systems are used to rapidly and inexpensively predict the effects of nanomaterials at the cellular level. Recent advances in the toxicity testing of nanomaterials are beginning to shed light on the characteristics, uptake and mechanisms of their toxicity in a variety of cell types. Once the nanomaterials have been satisfactorily characterized, the evaluation of their interactions with cells can be studied with microscopy and biochemical assays. The combination of viability testing, observation of morphology and the generation of oxidative stress provide clues to the mechanisms of nanomaterial toxicity. The results of these studies are used to better understand how the size, chemical composition, shape and functionalization may contribute to their toxicity. This chapter will introduce the reader to the impact of nanomaterials in the workplace and marketplace with an emphasis on carbon-based and metal-based nanomaterials, which are most commonly encountered. While most purified carbon nanomaterials were nontoxic to many cell lines, many metal nanoparticles (e.g., silver or manganese) were more toxic. Other side- effects of nanoparticle interactions with cells can also occur, such as increased branching and dopamine depletion. Further investigation into the characteristics, uptake and mechanisms of nanomaterial toxicity will continue to elucidate this fascinating and rapidly growing area of science.