Process developments in reactive extrusion or reactive compounding are largely carried out in closely intermeshing corotating twin-screw extruders. The aim of this article is to present an analytical process model for this reactor type in order to facilitate the design of screw geometry and the settings of process parameters. Taking simultaneously into account aspects of flow behavior, heat transfer, thermodynamics, physics, and chemistry, a powerful mathematical model has been developed which was compared with practical results (e.g., residence time, pressure buildup, drive energy, bulk temperature, and conversion) on lab and production scale machines. The experiments were mostly carried out for the anionic bulk polymerizations of nylon 6 and polystyrene. Furthermore the reactive bending of nylon 6 and polyethyleneterephthalate was examined. Based on these chemical systems the practical use of computer-aided process design will be discussed.