Studies of the uptake, biological fate, and toxicity of several metal oxide nanoparticles (NPs), such as Al2O3, TiO2, CeO2-x, and ZnO NPs undertaken in the European Project “Health Impact of Engineered Metal and Metal Oxide Nanoparticles: Response, Bioimaging and Distribution at Cellular and Body Level” are reviewed here. Metal oxide NPs are radiolabeled by direct proton bombardment of commercially available NPs or enriched during synthesis with 18O to generate 18F after-proton bombardment. Size, degree of aggregation, and zeta potential of the metal oxide NPs are studied in the presence of proteins and cell media. NP uptake and intracellular fate are followed by ion beam microscopy (IBM), transmission electron microscopy, confocal Raman microscopy and confocal laser scanning microscopy. IBM allows for the quantification of the intracellular dose of NPs. Cell viability studies and the immune response are studied “in vitro” in primary alveoli, and immortalized cell lines. Biodistribution studies in rodents are performed with positron emission tomography following different exposure routes: intravenous, oral, topical, and inhalation using radiolabelled NPs. Activity per organ is quantified for the different uptake routes and with the time.