Microbial endocrinology represents the intersection of 2 seemingly disparate fields, microbiology and neurobiology, and is based on the shared presence of neurochemicals that are exactly the same in structure in the host as well as in the microorganism. The ability of microorganisms not only to respond to but also to produce many of the same neurochemicals that are produced by the host, such as during periods of stress, has led to the introduction of this evolution-based mechanism which has a role in the pathogenesis of infectious disease as well as the microbiota-gut-brain axis. Production of neurochemicals by microorganisms usually employs the same biosynthetic pathways as those utilized by the host, indicating that acquisition of a neurochemical-based signaling system in the host may have been acquired due to lateral gene transfer from microorganisms. Such recognition of a common shared signaling system suggests that there is a common mechanistic pathway by which the host may interact with the microbiota in a bi-directional fashion influencing aspects of both disease and health. In the case of infectious disease pathogenesis, the consideration of a microbial endocrinology–based mechanism in which infectious bacteria can directly respond to host-derived neurochemicals such as those present during periods of stress has demonstrated, for example, that the prevalent use of catecholamine-based synthetic drugs in the clinical setting contributes to the formation of biofilms in indwelling medical devices leading to increased morbidity and mortality. At the same time, the ability of the microbiota to produce neurochemicals that constitute the host’s own neuronal signaling systems means that a common pathway exists for the microbiota to influence host neurophysiology. Currently, we have little understanding of the neurochemical environment of ruminants, whether that within the rumen microbiota or the host tissue. Application of a microbial endocrinology-based approach may lead us to the identification of novel mechanisms by which the ruminant interacts with its microbiota and thereby provide new approaches to health and disease management.