Oxidative stress is an unavoidable peril that aerobic organisms have to confront. Thus, it is not surprising that intricate strategies are deployed in an effort to fend the dangers associated with living in an O(2) environment. In the classical models of anti-oxidative defense mechanisms, a variety of stratagems including the reactive oxygen species (ROS) scavenging systems, the NADPH-generating enzymes and the DNA repair machineries are highlighted. However, it is becoming increasingly clear that metabolism may be intimately involved in anti-oxidative defence. Recent data show that metabolic reprogramming plays a pivotal role in the survival of organisms exposed to oxidative stress. Here, we describe how Pseudomonas fluorescens, the metabolically-versatile soil microbe, manipulates its metabolic networks in an effort to counter oxidative stress. An intricate link between metabolism and anti-oxidative defense is presented. P. fluorescens reconfigures its metabolic processes in an effort to satisfy its need for NADPH during oxidative insult. Seemingly, disparate metabolic modules appear to partner together to concomitantly fine-tune the levels of the anti-oxidant NADPH and the pro-oxidant NADH. Central to this shift in the metabolic production of the pyridine nucleotides is the increase in NAD kinase with the concomitant decrease in NADP phosphatase. The tricarboxylic acid cycle is tweaked in an effort to limit the formation of NADH. This metabolic redox-balancing act appears to afford a potent tool against oxidative challenge and may be a more widespread ROS-combating tactic than hitherto recognized.