Recent advances in medical research have revealed how humans rely on their microbiome for diverse traits and functions. Similarly, microbiomes of other higher organisms play key roles in disease, health, growth and development of their host. Exploring microbiome functions across kingdoms holds enormous potential to understand common mechanisms and concepts underlying microbiome assembly and microbial processes that sustain life of Eukaryotes. The gut and plant rhizosphere are both open systems with large surface areas overpopulated with microbes. Despite distinct differences in microbiome composition, these two ecosystems share striking similarities in microbiome functions related to nutrient acquisition, immune system modulation and protection against infections. We also discuss how humans and plants exchange microbes, for better or for worse. We propose that adopting ecological theory, combined with modeling and synthetic microbial ecosystems, provides a promising strategy to identify host traits and cues involved in microbiome assembly on and in Eukaryotes