Systems biology is based on a mathematized understanding of molecular biological processes. Because genetic networks are so complex, a system understanding is required that allows for the appropriate modelling of these complex networks and its products up to the whole-cell scale. Since 2000 standardizations in modelling and simulation techniques have been established to support the community-wide endeavors for whole-cell simulations. The development of the Systems Biology Markup Language (SBML), in particular, has helped systems biologists achieve their goal. This paper explores the current developments of modelling and simulation in systems biology. It discusses the question as to whether an appropriate system understanding has been developed yet, or whether advanced software machineries of whole-cell simulations can compensate for the lack of system understanding.