In 2005, a survey compared a number of commercial PBPK software available at the time, mainly focusing on ‘ready to use’ modelling tools. Since then, these tools and software have been further developed and improved to allow modellers to perform WB-PBPK modelling including ADME processes at a high level of sophistication. This review presents a comparison of the features, values and limitations of both the ‘ready to use’ software and of the traditional user customizable software that are frequently used for the building and use of PBPK models, as well as the challenges associated with the various modelling approaches regarding their current and future use. PBPK models continue to be used more and more frequently during the drug development process since they represent a quantitative, physiologically realistic platform with which to simulate and predict the impact of various potential scenarios on the pharmacokinetics and pharmacodynamics of drugs. The ‘ready to use’ PBPK software has been a major factor in the increasing use of PBPK modelling in the pharmaceutical industry, opening up the PBPK approach to a broader range of users. The challenge is now to educate and to train scientists and modellers to ensure their appropriate understanding of the assumptions and the limitations linked both to the physiological framework of the ‘virtual body’ and to the scaling methodology from in vitro to in vivo (IVIVE).