The NADPH oxidase (NOx) family comprises NOX1-5 and DUOX1, DUOX2, mainly localized on the cell membrane and endomembrane, generating reactive oxygen species (ROS) by transferring electrons to oxygen molecules. They are expressed in immune cells, the cardiovascular system, and the nervous system, regulating cell proliferation, differentiation, death, and immune responses. Activation of the NOX family involves multiple signaling pathways, such as PKC, MAPK, and PI3K/Akt. Gene-specific expression and mutations affecting ROS production are associated with various diseases, including chronic inflammation, neurodegenerative diseases, cardiovascular diseases, and cancer.