Computational modelling approaches can nowadays build large-scale simulations of cellular behaviour based on data describing detailed molecular level interactions, thus performing the space- and time-scale integrations that would be impossible just by intuition. Recent progress in the development of both experimental methods and computational tools has provided the means to generate the necessary quantitative data and has made computational methods accessible even to non-theorists, thereby removing a major hurdle that has in the past made many experimentalists hesitate to invest serious effort in formulating quantitative models. We describe how computational biology differs from classical bioinformatics, how it emerged from mathematical biology and elucidate the role it plays for the integration of traditionally separated areas of biomedical research within the larger framework of Systems Biology.