This chapter introduces the principles and development procedures for physiologically based pharmacokinetic (PBPK) models, and their application for nanoparticle toxicity studies. PBPK models describe the concentration-time or mass-time profiles of chemicals or nanoparticles in individual tissues and organs within the body. They have been used mostly for toxicology and pharmacology studies of small molecules, and their application for nanoparticles are in the early stages. Due to the biodistribution differences between nanoparticles and small molecules, modification may be necessary to build PBPK models for nanoparticles. PBPK models for nanoparticles may be applied to biodistribution predictions, data extrapolation, and property-biodistribution relationships, and, thus, can be a powerful tool in toxicity evaluation.