Recent years have brought a changing imperative in life sciences sparked by the revolution of genomic tools to study the molecular composition and functional organization of organisms. The development of next-generation sequencing changed our understanding of microbial diversity associated with organisms and environments. There are now a multitude of studies that support the notion that a host-specific microbiome associates with multicellular organisms and provides functions related to metabolism, immunity, and environmental adaptation, among others. Consequently, interactions and communication mechanisms of members in this metaorganism presumably play a major role in maintaining host health, microbiome stability, and resilience to environmental disturbance. It is currently debated whether metaorganisms constitute a hologenome as the unit of selection or whether metaorganisms are comprised of distinct entities that evolve independently. This plenary presentation will present and discuss recent efforts to investigate metaorganism function and evolution, and how the appreciation of host-microbe interactions provides new insight to host biology in light of the microbiome.