In chemical process operation, the purpose of control is to achieve optimal process operation despite the presence of significant uncertainty about the plant behavior and disturbances. Tracking of set-points is often required for lower-level control loops, but on the process level in most cases this is not the primary concern and may even be counterproductive. In this paper, different approaches how to realize optimal process operation by feedback control are reviewed. The emphasis is on direct optimizing control by optimizing an economic cost criterion online over a finite horizon where the usual control specifications in terms of, e.g., product purities enter as constraints and not as set-points. The potential of this approach is demonstrated by its application to a complex process which combines reaction with chromatographic separation. Issues for further research are outlined in the final section. (c) 2006 Elsevier Ltd. All rights reserved.