Oxygen has a great impact on the metabolism and physiology of microorganisms. It serves as the most efficient terminal electron acceptor to drive the energy conservation process of cellular respiration and is required in many biosynthetic reactions. Bacteria encounter oxygen fluctuation and limitation during their growth in both natural ecological niches and in laboratory vessels. In response to oxygen limitation, facultative bacteria undergo substantial metabolic reprogramming to switch from the aerobic respiration to either anaerobic respiration, fermentation, or photosynthesis. Two key factors determine the metabolic pathways bacteria adopt under oxygen deprived microaerobic and anaerobic conditions: maximal energy conservation and redox homeostasis. In this chapter, we first describe how the fulfillment of these two key factors governs the metabolic reprogramming of facultative bacteria and how the process is tightly controlled by several global regulatory factors: FNR, ArcBA, as well as NarL and NarP. We then utilizes fermentation of glycerol, a large surplus byproduct of biodiesel industry, as an example to illustrate how environment, process, and strain based approaches can be exploited to manipulate and engineer the anaerobic metabolic pathways so that desirable fermentation products can be achieved with optimal yield.