Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals, being used in almost all industry branches and many consumer products. The use of many legacy PFAS is being reduced due to their high persistence and hazardous effects. Therefore, novel PFAS are increasingly used for numerous industrial applications, whereas at the same time there is no or only few data on their toxicity. Due to the large number of PFAS, it is impossible to perform hazard characterization on all PFAS based on experimental data. Here in silico models are a helpful tool to obtain hazard insights and to prioritize experiments accordingly. The nuclear receptor PPARα plays an essential role in lipid metabolism and is being activated by fatty acids. However, it has also been shown to be activated by many PFAS.