In this chapter, we review the most important aspects of nanomaterial toxicity as established from in vitro, in vivo and epidemiological studies. Owing to their minute size, nanoparticles can enter the body via various routes and can initially interact with diverse endogenous biomolecules forming a “protein corona”. Subsequently, they can be distributed to various organs where they can accumulate, and enter cells and cell organelles, disrupting cell physiology. Depending on their size, type of material, morphology and surface functionalization, some nanomaterials can have adverse effects on human health. Exposure to toxic levels of nanoparticles can lead to cardiovascular, respiratory, neurological and immune disease. Some nanoparticles may be implicated in the development of cancers. Nanomaterials have many unique properties compared to bulk formulations of the same material, such as enhanced magnetic, catalytic, optical, electrical, and mechanical properties. As a result, the toxicity of each nanomaterial cannot be easily predicted based on the bulk material’s properties; for example, a non-toxic material in bulk form might become toxic in nanomaterial form. The application of nanomaterials in all aspects of life and science, while having enormous potential benefits, can lead to human health problems and environmental pollution. It would be ideal to have preliminary toxicity assessment of nanoparticles before their incorporation into marketed products.