The rapid development of nanotechnology requires the production of nanoparticles which are found in numerous novel products. To reduce the number of animal tests during the assessment of lung toxicity of airborne nanoparticles in vitro exposure systems and lung specific bioassays have been developed. The reproducible application of bioassays for exposure of lung cells at the air-liquid interface promises a higher efficiency and cost reductions in toxicological testing. Despite significant progress of the exposure technology and fundamentals of bioassays a stringent validation of the in vitro versus in vivo tests is still lacking.