Although for decades nearly all pharmaceuticals have been purified by crystallization, there have been a disproportionate number of problems associated with the operation and control of these processes. This paper provides an overview of the recent advances in model-based and model-free (direct design) approaches to control the crystallization of pharmaceuticals, treating both antisolvent and cooling crystallization. A model-based combined technique which simultaneously controls the antisolvent addition rate and the cooling profile is presented. A population balance model of the combined cooling-antisolvent addition system is developed and a moments model is used in optimal control strategies with various objective functions. The simulation and experimental results show the advantages of the combined approach. (C) 2008 Elsevier Ltd. All rights reserved.