The goal of this Methods Collection is to highlight the translational applications of companion animals, large livestock, and other laboratory animal species to understand immunology in health and disease. Despite many decades of scientific research, the vast majority of which focused on rodent studies, we continue to suffer from multiple diseases for which there are no immunization strategies or treatments. This is owing to the poor translation of results from rodents to humans. Murine models offer remarkable research advantages in several diseases due to their manageability, cost-effectiveness, and versatility; however, different research groups in recent years have singled out their limitations in evaluating the response to treatment in various diseases in human medicine. Therefore, to an extent, there is an increasing demand for the use of novel animal models that better resemble the human pathophysiology. By bringing together human, mouse, and veterinary immunologists, we could provide novel and translational insights to address important biological questions. Systematic analysis of the transcriptome and proteome of different species has greatly advanced in recent years and provides a valuable window to the biology community. We highlight the importance of future multi-omic studies in animal models, the findings of which may also apply to human and veterinary research. In keeping with the One Health concept, and the increasing scientific evidence of the potential benefits of the bidirectional cross-species translational application of biological data derived from different species, the goal of this collection is to highlight the translational applications of these systems to understand immunology in health and disease.