The separation and the purification of proteins has been an important field for research. Indeed, the separation of one protein from all others, in the biological environment, is typically the most difficult aspect of protein purification. Separation steps exploit differences in protein molecular size, physicochemical properties and binding affinity. The separation and the purification of protein in this review focus on protein crystallization. The research activities in protein crystallization were discussed based on engineering concepts of thermodynamics, kinetics and mass transport. Process design and engineering problem are also presented. (C) 2009 Elsevier B.V. All rights reserved.