The delivery of therapeutic agents is characterized by numerous challenges including poor absorption, low penetration in target tissues and non‐specific dissemination in organs, leading to toxicity or poor drug exposure. Several nanomedicine strategies have emerged as an advanced approach to enhance drug delivery and improve the treatment of several diseases. Numerous processes mediate the pharmacokinetics of nanoformulations, with the absorption, distribution, metabolism and elimination (ADME) being poorly understood and often differing substantially from traditional formulations. Understanding how nanoformulation composition and physicochemical properties influence drug distribution in the human body is of central importance when developing future treatment strategies. A helpful pharmacological tool to simulate the distribution of nanoformulations is represented by physiologically based pharmacokinetics (PBPK) modelling, which integrates system data describing a population of interest with drug/nanoparticlein vitrodata through a mathematical description ofADME. The application ofPBPKmodels for nanomedicine is in its infancy and characterized by several challenges. The integration of property–distribution relationships inPBPKmodels may benefit nanomedicine research, giving opportunities for innovative development of nanotechnologies.PBPKmodelling has the potential to improve our understanding of the mechanisms underpinning nanoformulation disposition and allow for more rapid and accurate determination of their kinetics. This review provides an overview of the current knowledge of nanomedicine distribution and the use ofPBPKmodelling in the characterization of nanoformulations with optimal pharmacokinetics.Linked ArticlesThis article is part of a themed section on Nanomedicine. To view the other articles in this section visithttp://dx.doi.org/10.1111/bph.2014.171.issue‐17