Enhanced molecular reaction control is one of the major breakthrough routes for achieving maximally sustainable and efficient chemical processes. Numerous fundamental works on this topic can be seen in literature and it is now the key challenge to advance them in an interdisciplinary way towards the industrial implementation of what can be envisaged as Perfect Reactors. In such reactors control of the molecular alignment and geometry of collisions as well as selective and efficient activation of the reacting molecules are the central issues to be tackled. In the paper the current status of molecular-level control of chemical transformations is reviewed by describing methods for alignment and orientation control such as nanostructured confinement and the application of external fields. The latter method is also instrumental for local and selective energy supply in chemical processes. Finally, the use of transient operation can lead to more efficient processing, also on the molecular level. In order to realize the Perfect Reactors concepts by 2050 research efforts should be based on simultaneous and multi-scale addressing of the four fundamental domains of Process Intensification: spatial, thermodynamic, functional and temporal. (C) 2011 Elsevier B.V. All rights reserved.