Phagocytic leukocytes, when appropriately stimulated, display a respiratory burst in which they consume oxygen and produce superoxide anions. Superoxide is produced by the phagocyte NADPH-oxidase system which is a multiprotein complex that is dissociated in quiescent cells and is assembled into the functional oxidase following stimulation of these cells. Also associated with the respiratory burst is the generation of other reactive oxygen species. The identity of components of the NADPH-oxidase system and their interactions are known in considerable molecular detail. Understanding of the regulation of superoxide production is less well known. This review also points out the important role of microscopy in complementing biochemical studies to understand better the cell biology of the phagocyte respiratory burst.