Crocodilians are an ancient lineage composed of long-lived, top trophic carnivores and that are of evolutionary, economic, and ecological importance. Recent advances and anecdotal observations, along with evolutionary insights, have increased interest into the immune system of crocodilians. Immunocompetence, the ability to mount an effective immune response following pathogenic exposure, is of paramount importance in the life history of an organism. However, this ability may be regulated by a number of stressors including infection, toxicant exposure, climate, reproduction, and various other biotic and abiotic factors. Physiological responses to stressors may be varied, including activation of the fight or flight response, alterations in metabolic rate, perturbations in physiological processes, or activation of the hypothalamic-pituitary-adrenal (HPA) axis, however, all responses function to preserve and reinstate homeostasis following stressor stimulation. Whilst the definition of a stressor is usually consensually defined, the definition of the stress response following stressor stimulation is more ambiguous. Some authorities, however, now suggest restriction in defining stress to only those responses that are mediated by the HPA axis culminating in production of glucocorticoids (GCs). Crocodilians represent an interesting lineage in which to investigate the effects of stressors on the immune system because of their slow evolutionary rate, basal phylogenetic position among archosaurs, role as economic commodities, and high trophic placement. In particular, crocodilians may serve as indicators of habitat quality, thus, examination of how exogenous toxicants affect their immune systems may provide insight into other species and the overall health of the environment. Furthermore, many crocodilians, such as the American alligator, are keystone species, so investigations of stressors and their impact on immune function are necessary for conservation. Some crocodilians, like the saltwater crocodile and alligator, represent important economic commodities providing monetary incentives for conservation through sustainable use. However, such increased interaction may increase susceptibility to zoonoses. In this dissertation, I investigate the immune system of crocodilians and how stressors may influence the immune system through the action of toxicants, microbial disease, and agricultural production settings.