The production of reactive oxygen and reactive nitrogen intermediates is an important host defense mechanism mediated in response to infection by bacterial pathogens. Not surprisingly, intracellular pathogens have evolved numerous defense strategies to protect themselves against the damaging effects of these agents. In enteric bacteria, exposure to oxidative or nitrosative stress induces expression of numerous pathways that allow the bacterium to resist the toxic effects of these compounds during growth in the host. In contrast, members of pathogenic mycobacterial species, including the frank human pathogens Mycobacterium tuberculosis and Mycobacterium leprae, are dysfunctional in aspects of the oxidative and nitrosative stress response, yet they remain able to establish and maintain productive acute and persistent infections in the host. This article reviews the current knowledge regarding reactive oxygen and nitrogen intermediates, and compares the adaptative mechanisms utilized by enteric organisms and mycobacterial species to resist the bactericidal and bacteriostatic effects resulting from exposure to these compounds.