Metabolism is defined as the full complement of chemical transformations in living systems. Systems biology techniques are increasingly being used to elucidate and quantify the full range of molecules (e.g., metabolite concentrations) and transformations (e.g., reaction fluxes) at play. In this talk we will explore how computations can shed light onto the interdependence, fragility and redundancy of metabolism in living systems. We will discuss how we can pinpoint the essential core of genes needed to ensure life's processes to better understand the organizational principles of metabolism and provide insights into the design of minimal organisms. We will next explore how we can speed up the process of building organism-specific metabolic models by automatically filling in connectivity gaps and restoring consistency with gene essentiality experiments. With the metabolic reconstructions in place, we will next describe how we can use computations to decipher metabolic flows given NMR or GC/MS spectra derived from ¹³C labeling experiments. Optimization based techniques will finally be illustrated for strain optimization case-studies by classifying all fluxes in a metabolic model depending upon whether or not they must increase, decrease, or become equal to zero to meet a pre-specified overproduction target.