The liver is the most important organ for drug metabolism and determines pharmacokinetics for most medicines. It is also a target for therapeutics for the treatment of a variety of diseases, such as hepatitis, non-alcoholic fatty liver disease, cirrhosis and hemochromatosis. In addition, hepatotoxicity remains a significant safety issue during drug discovery and development. Quantitative, model-based approaches have contributed to scientific advancement in all these areas, ranging from better understanding of liver (patho)physiology as a determinant of inter- and intra-individual pharmacokinetics (PBPK) to identification and validation of novel targets for drug treatment using quantitative systems pharmacology (QSP). The Liver Virtual Issue CPT:PSP is a resource of state-of-the-art original research, reviews, and tutorials of pharmacometrics and systems pharmacology science and applications in the field of hepatology.