In this chapter inhalation of nanomaterials and its main effects on the lung are discussed. The behavior of inhaled particles differs significantly from that of inhaled gaseous or volatile compounds. The deposition of solid material in the respiratory tract is dependent on material-specific physicochemical characteristics and host factors. Three distinct mechanism of deposition are described: impaction, sedimentation, and diffusion. Particles between 10-50 nm are deposited mainly in the alveoli, smaller and larger ones are more efficiently deposited in the higher regions. Fibers with a small diameter can also penetrate deep into the lungs, even a small portion of long fibers (≫20 μm) can enter the alveolar space. Clearance: The removal of solid material from the lungs is carried out by two distinct mechanisms. The mucociliary escalator, a very efficient mechanism, dominates the clearance from the airways and the nose; in the alveolar region the clearance predominantly takes place by macrophage phagocytosis. Nanosized particles are more likely to hamper the clearance resulting in a higher burden, possibly amplifying the observed effect. The persistence of material in the lung also depends on the material-specific biodurability. What makes nanoparticles dangerous? The biological effects of nanomaterials do not just depend on the intrinsic toxicity of the material. Parameters such as size, surface area, the charges carried by the particle in contact with the cell membranes and the chemical reactivity also play a role. The primary effects observed after inhalation of nanomaterials are the induction of oxidative stress and inflammation. Extrapulmonary effects of inhaled nanoparticle: Inhaled ultrafine (nanoparticles) particles probably can be translocated from the lumen of the lung into the systemic circulation and have a direct effect on, e.g., blood clotting. It has also been observed that nanoparticles can, via the olfactory bulb, enter the brain, and is possibly linked to neurological disorders.