Abstract The rumen microbiome has a critical role in multiple facets of ruminant livestock production. It is well known that the rumen microbiome is integral to animal performance through impacts on feed efficiency, greenhouse gas production, volatile fatty acid production, and numerous aspects of animal health. Therefore, understanding factors that influence the rumen microbiome at various stages of the production cycle and the interactions with other microbial niches and physiological processes is a critical area of research to aid in the goal of improving livestock performance. Our research objectives have focused on 3 primary general areas including 1) to characterize and understand the potential pathways of early gut colonization from conception throughout gestation, 2) implications of varying gestational perturbations on rumen microbiome development and calf performance post-weaning, and 3) understand the connections between the rumen microbiome and the microbiomes of the reproductive tract, blood, and respiratory tract. We hypothesize that strategies to program the rumen microbiome early in life may have lasting impacts on host performance specific to feed efficiency, reproductive fitness, and have implications on high altitude disease. These effects may not be a direct relationship between the rumen microbiome and host response, but rather through a total system level response that has the rumen microbiome as a key player in that cascade. The rumen microbiome has the potential to impact numerous aspects of host performance, as such, it is imperative that research continues to elucidate its role in host physiology and the development of intervention mechanisms to initiate specific responses in the rumen microbiome to improve downstream host response.