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Crystallization is recognized among structural biologists as a necessary process before three-dimensional structure can be solved at an atomic level. Crystallization has a dose of mysticism among protein chemist. Some treats it as an “art” and others as “black magic”. These concepts aroused from a limited knowledge in the physical chemistry of proteins in solution. Crystallization appears only in a metastable state. To define crystallization conditions the experiments are guided either by a chance search or by dedicated factorial design. Here we will briefly describe a factorial design method to rationally approach the metastable state. In summary, there is nothing mysterious in crystallization of biological macromolecules, and the success can often be achieved within a limited number of experiments.