As product life cycles are declining, minimizing the set-up and start-up times of machines and part programs are of increasing importance. Today, it is possible to reduce the time required for setting up, testing and debugging of the PLC programming of machines as well as the MES control of entire production lines by using real-time hardware in the loop simulation (HiLS). Synchronization, logical, kinematic and dynamic behavior as well as the material flow can all be taken into account during the concurrent set-up of machine controls using virtual prototype before the machine or production line is physically available. Based on these developments, machine models computed on the control PC in real-time will open up new possibilities in the future. On the one hand, control integrated testing and optimization of NC part programs can be performed including collision detection and avoidance, material removal computation, energy consumption prediction and deviation detection and compensation. On the other hand, advanced model based control algorithms can be built around real time simulation models that take into account the varying dynamic behavior of machines over their range of motion.