In systems biology, computer simulation of the biochemical networks of a microbial cell is a powerful method to predict their function and phenotype under different culture conditions and genetic modifications. Construction of a virtual microbe, a generic mathematical model of cell growth and metabolism, can be an ambitious but realistic project. It would enable the rational design of a biochemical network to enhance the production of useful metabolites and proteins. However, there exist critical problems, such as parameter uncertainty, mechanism complexity and high dimensionality of the model. We would like to review the dynamic models of the biochemical networks with their problems, providing insight into developing a virtual microbe.