Technical Abstract: Nontyphoidal Salmonella encephalopathies (NSTE) represent a sporadic but serious manifestation of salmonellosis. Published studies are predominantly devoted to cases involving humans. The intent of this review is to identify common themes in human NSTE cases and to also explore the bases for NSTE in cattle where it may be an emerging phenomenon. In human cases, there appears to be an immunologic basis for NSTE. Children, particularly infants, are the most commonly afflicted patients, which is not surprising given their underdeveloped immune systems. HIV patients are the second largest subpopulation of human NSTE, further supporting the immune component. In cattle, however, the mitigating factor appears to indirectly involve the immune system. That is, stress appears to be the inducer in bovine NSTE. This statement is based on our findings that, using three different Salmonella strains involved in previous anecdotal reports of bovine NSTE, the disease could only be reproduced in calves using a norepinephrine-based stress model. This review identifies a potential commonality for many NSTE cases and provides the first characterization of Salmonella encephalopathy in livestock.