The program PottersWheel has been developed to provide an intuitive and yet powerful framework for data-based modeling of dynamical systems like biochemical reaction networks. Its key functionality is multi-experiment fitting, where several experimental data sets from different laboratory conditions are fitted simultaneously in order to improve the estimation of unknown model parameters, to check the validity of a given model, and to discriminate competing model hypotheses. New experiments can be designed interactively. Models are either created text-based or using a visual model designer. Dynamically generated and compiled C files provide fast simulation and fitting procedures. Each function can either be accessed using a graphical user interface or via command line, allowing for batch processing within custom Matlab scripts. PottersWheel is designed as a Matlab toolbox, comprises 250,000 lines of Matlab and C code, and is freely available for academic usage at www.potterswheel.de .