Purposeful generation of superoxide by a specialized NADPH oxidase has, until recently, been considered the exclusive property of phagocytes in their immunologic mission to kill invading microorganisms. However over the last 5 years, the existence of the NOX family of NADPH oxidases, comprising 7 homologues including the phagocyte NADPH oxidase, has been recognized. These homologues are expressed in a variety of different tissues including the gastrointestinal tract, the vascular system, kidney, thyroid, lung, lymphoid tissues, testis and the inner ear. Accordingly, the proposed physiological functions of these enzymes are likewise diverse and include epithelial cell host defense, maintenance of vascular tone, regulation of hormone biosynthesis, and modulation of cell proliferation and differentiation. The enzymes are likely to be involved in a variety of disease processes from immune deficiencies and hypothyroidism to atherosclerosis and vestibular dysfunction.