NADPH oxidase (NOX) is a transmembrane enzyme that is located in intracellular organelles. NADPH oxidase (NOX) enzymes are membrane-bound proteins that catalyze the conversion of oxygen to superoxide. There are a number of isoforms, NOX1-5 and dual oxidases 1 and 2 (DUOX1-2), which have diverse functions. NOX1, NOX2, NOX4, and NOX5 are expressed in human vascular tissue. NOX1 and NOX2 are regulated by cytosolic components loosely termed as activators or organizers, which are generally recruited to the membrane components following cellular stimuli to assemble an active NOX. Molecular switch from NOX1 to NOX2 in colon cancer cells induces ROS production and subsequently enhances MMP-7 expression by deactivating AMPK. Vascular NOX4 is a multifarious NADPH oxidase. NOX4 is a hydrogen peroxide-generating oxygen sensor.