Physiology-based pharmacokinetic models (PBPK) describe adsorption, distribution, metabolisation and excretion of drugs in the human body based on a large amount of prior physiological knowledge. Specific physiological information quantifying for example blood flow rates or relative tissue-specific gene-expression is explicitly provided in the structure of PBPK models. Most other parameters can be calculated from the physicochemical properties of the compound which is under investigation such as the lipophilicity and the molecular weight. PBPK models can in particular be used to mechanistically investigate the different processes underlying drug pharmacokinetics. Using the software PK-Sim, we here provide an introduction to PBPK modelling which allows the user to independently implement a first model model.