A progressive rise of oxidative stress due to the altered reduction–oxidation (redox) homeostasis appears to be one of the hallmarks of the processes that regulate gene transcription in physiology and pathophysiology. Reactive oxygen (ROS) and nitrogen (RNS) species serve as signaling messengers for the evolution and perpetuation of the inflammatory process that is often associated with the condition of oxidative stress, which involves genetic regulation. Changes in the pattern of gene expression through ROS/RNS-sensitive regulatory transcription factors are crucial components of the machinery that determines cellular responses to oxidative/redox conditions. Transcription factors that are directly influenced by reactive species and pro-inflammatory signals include nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1α (HIF-1α). Here, I describe the basic components of the intracellular oxidative/redox control machinery and its crucial regulation of oxygen- and redox-sensitive transcription factors such as NF-κB and HIF-1α.