The loss of antibiotics as a tool to improve feed efficiency in poultry production has increased the urgency to understand how the microbiota interacts with animals to impact productivity and health. Modulating and harnessing microbiota-host interactions is a promising way to promote poultry health and production efficiencies without antibiotics. In poultry, the microbiome is influenced by many host and external factors including host species, age, gut compartment, diet, and environmental exposure to microbes. Because so many factors contribute to the microbiota composition, specific knowledge is needed to predict how the microbiome will respond to interventions. The effects of antibiotics on microbiomes have been well documented, with different classes of antibiotics having distinctive, specific outcomes on bacterial functions and membership. Non-antibiotic interventions, such as probiotics and prebiotics, target specific bacterial taxa or function to enhance beneficial properties of microbes in the gut. Beneficial bacteria provide a benefit by displacing pathogens and/or producing metabolites (e.g., short chain fatty acids or tryptophan metabolites) that promote poultry health by improving mucosal barrier function or immune function. Microbiota modulation has been used as a tool to reduce pathogen carriage, improve growth, and modulate the immune system. An increased understanding of how the microbiota interacts with animal hosts will improve microbiome intervention strategies to mitigate production losses without the need for antibiotics.