Nitric oxide (NO) is a simple diatomic molecule that is involved in a wide range of biological processes. In mammalian systems, nitric oxide is employed in the regulation of blood flow, the immune response, and involved in a variety of other healthy and pathological processes. As a number of NO's functions have disparate effects, it is interesting to explore how biological systems are “engineered” to exploit nitric oxide biochemistry. During the course of our research, we have examined how reactant flux and transport processes influence NO's reactivity and dispersal in the circulatory system. In particular, we have explored how the rate of NO delivery affects the reactions between NO and hemoglobin (Hb). When NO is delivered rapidly to an oxygenated Hb system, the flux through the relatively slow reaction between NO and oxidized Hb is increased; resulting in an unexpected product distribution. Additionally, we have computationally explored how compartmentalization facilitates NO transport in resistance vessels. Most recently, we have explored the interactions between NO and E. coli's genomic program. Using a chemogenomic approach, we have identified a heretofore unknown mechanism through which NO induces bacteriostasis. NO elicits bacteriostasis by inhibiting IlvD activity, which in turn leads to branched-chain amino acid (BCAA) depletion and thus inhibition of translation and growth. As mammals do not synthesize BCAAs, inhibition of IlvD activity may have served to foster NO's role in the immune system. Additionally, we identified the iron-sulfur cluster repair system as a key component of E. coli's defense network.