Bacteria, including those that are pathogenic, have been generally classified according to their ability to survive and grow in the presence or absence of oxygen: aerobic and anaerobic bacteria, respectively. Strict aerobes require oxygen to grow (e.g., Neisseria), and strict anaerobes grow exclusively without, and do not survive oxygen exposure (e.g., Clostridia); aerotolerant bacteria (e.g., Lactobacilli) are insensitive to oxygen exposure. Facultative anaerobes (e.g., E. coli) have the unique ability to grow in the presence or in the absence of oxygen and are thus well-adapted to these changing conditions, which may constitute an underestimated selective advantage for infection. In the WHO antibiotic-resistant ‘priority pathogens’ list, facultative anaerobes are overrepresented (8 among 12 listed pathogens), consistent with clinical studies performed in populations particularly susceptible to infectious diseases. Bacteria aerobic respiratory chain plays a central role in oxygen consumption, leading to the formation of hypoxic infectious sites (infectious hypoxia). Facultative anaerobes have developed a wide diversity of aerotolerance and anaerotolerance strategies in vivo. However, at a single cell level, the modulation of the intracellular oxygen level in host infected cells remains elusive and will be discussed in this review. In conclusion, the ability of facultative bacteria to evolve in the presence or the absence of oxygen is essential for their virulence strategy and constitute a selective advantage