Complete metabolic maps are currently available for a number of important bacteria. Even when these maps are not experimentally confirmed, the topology of the metabolic network can be reconstructed from the genome sequence. Despite this extensive information, we still lack a good understanding of metabolic adaptations, the interactions of metabolism with gene regulation and tools for predicting the metabolic consequences of modifying the metabolic or genetic regulatory network of a bacterium. This chapter will briefly review current methods for analyzing bacterial metabolism from topological models and steady state techniques, such as flux balance analysis, to dynamical models using ordinary differential equations. Even though still incomplete, these models can predict the metabolic behavior of modified organisms. Using these tools, we can create novel metabolic pathways or optimize the yield of a desired metabolite. Focusing on Escherichia coli, we present examples of successful metabolic engineering using such systems-wide, rational approaches, integrating modeling and experiments. The conjunction of systems biology to metabolic engineering yields new insights into the fundamental functioning of the cell and opens the path to the biological production of a large variety of commodity chemicals.