The best method for process control is the use of model-based solutions, based on process analytical technology for online monitoring of critical process variables, product quality attributes, or a holistic process state estimation. Mechanistic models as well as data-driven techniques are essential for real-time process monitoring. Their main characteristics, advantages and disadvantages, and the link between both are discussed as well as the synergetic effects, benefits, and drawbacks resulting from their combination. Aspects and differences of the computational model life cycle management are highlighted.