While petroleum provides the majority of fuels and chemicals used today, the unreliable supply, the fluctuation of price, and the negative environmental impact of its use have stimulated significant interests to replace petroleum with alternative sources. Existing schemes include the use of plant biomass or algae to produce ethanol, biodiesel, and some chemicals. Despite the success of these leading processes, next-generation biorefinery should consider other options as the starting materials, manufacturing schemes, and the product itself. To accomplish these goals, synthetic pathways in cells are to be re-engineered to produce various chemicals and fuels. In this talk, we will discuss principles for re-wiring metabolic networks in living organisms, including biochemical, thermodynamic, and kinetic considerations.