The biological reduction of N(2) is catalyzed by nitrogenase, which is irreversibly inhibited by molecular oxygen. Cyanobacteria are the only diazotrophs (nitrogen-fixing organisms) that produce oxygen as a by-product of the photosynthetic process, and which must negotiate the inevitable presence of molecular oxygen with an essentially anaerobic enzyme. In this review, we present an analysis of the geochemical conditions under which nitrogenase evolved and examine how the evolutionary history of the enzyme complex corresponds to the physiological, morphological, and developmental strategies for reducing damage by molecular oxygen. Our review highlights biogeochemical constraints on diazotrophic cyanobacteria in the contemporary world.