The intestine performs the critical roles of nutrient acquisition, tolerance of innocuous and beneficial microorganisms, while retaining the ability to respond appropriately to undesirable microbes or microbial products and preventing their translocation to more sterile body compartments. Various components contribute to antimicrobial defenses in the intestine. The mucus layer(s), antimicrobial peptides and IgA provide the first line of defense, and seek to trap and facilitate the removal of invading microbes. If breached, invading microbes next encounter a single layer of epithelial cells and, below this, the lamina propria with its associated immune cells. The gut immune system has developmental stages, and studies from different species demonstrate that innate capability develops earlier than acquired. In addition, various factors may influence the developmental process; for example, the composition and activity of the gut microbiota, antimicrobials, maternally derived antibodies, host genetics, and various stressors (e.g. feed deprivation). Therefore, it is clear that particularly younger (meat-producing) animals are reliant on innate immune responses (as well as passive immunity) for a considerable period of their productive life, and thus focusing on modulating appropriate innate responses should be an intervention priority. The gut microbiota is probably the most influential factor for immune development and capability. Interventions (e.g. probiotics, prebiotics, antibodies, etc.) that appropriately modulate the composition or activity of the intestinal microbiota can play an important role in shaping the desired functionality of the innate (and acquired) response. In addition, innate immune mediators, such as toll-like receptor agonists, cytokines, etc., may provide more specific ways to suitably modulate the response. A better understanding of mucosal immunology, signaling pathways, and processes, etc., will provide even more precise methods in the future to boost innate immune capability and minimize any associated (e.g. nutrient) costs. This will provide the livestock industry with more effective options to promote robust and efficient productivity.