The hologenome is an evolutionary concept in which a host and its associated microorganisms together compose a single unit of selection, known as the holobiont. Bidirectional interactions between the host and the microbiota genomes shape complex phenotypes and have implications for evolution, adaptation, and breeding. Advances in multi-omics technologies now enable a comprehensive investigation of host-microbiota interactions, allowing their integration into breeding programs and revealing novel targets for enhancing animal health, productivity, and sustainability in agriculture.