With the great interests in the discovery and development of drug products containing nanoparticles, there is a great demand of quantitative tools for assessing quality, safety, and efficacy of these products. Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches provide excellent tools for describing and predicting in vivo absorption, distribution, metabolism, and excretion (ADME) of nanoparticles administered through various routes. PBPK modeling of nanoparticles is an emerging field, and more than 20 PBPK models of nanoparticles used in pharmaceutical products have been published in the past decade. This review provides an overview of the ADME characteristics of nanoparticles and how these ADME processes are described in PBPK models. Recent advances in PBPK modeling of pharmaceutical nanoparticles are summarized. The major challenges in model development and validation and possible solutions are also discussed.