Challenges in real-time process optimization mainly arise from the inability to build and adapt accurate models for complex physico-chemical processes. This paper surveys different ways of using measurements to compensate for model uncertainty in the context of process optimization. Three approaches can be distinguished according to the quantities that are adapted: model-parameter adaptation updates the parameters of the process model and repeats the optimization, modifier adaptation modifies the constraints and gradients of the optimization problem and repeats the optimization, while direct input adaptation turns the optimization problem into a feedback control problem and implements optimality via tracking of appropriate controlled variables. This paper argues in favor of modifier adaptation, since it uses a model parameterization and an update criterion that are well tailored to meeting the KKT conditions of optimality. These considerations are illustrated with the real-time optimization of a semi-batch reactor system. (C) 2009 Elsevier Ltd. All rights reserved.