Abstract: Characterizing drug transport and distribution within the brain can help predict drug effect and adverse drug reaction during new drug development. However, a major hurdle exists in directly measuring drug concentrations in human brain. Physiologically-based pharmacokinetic (PBPK) modelling of drug transport and distribution in brain tissue is highly beneficial for predicting human brain concentrations. In this article, physiological properties that affect drug transport and distribution within the brain was reviewed. Existing PBPK models of the brain tissue as well as their applications in new drug development were also overviewed.