Organisms and their microbiomes form a unified whole: the holobiont. I have long been fascinated by how the microbiome, acquired after birth, can change over time while still maintaining communication with the host to function as a single organism. To study this, I use the Five R Framework—Rules, Responses, Repercussions, Recovery, and Resonance—to guide my research on host–microbiome interactions. Together, these themes capture how microbiomes are assembled, how they shift under ecological change, how those shifts impact hosts and ecosystems, how communities recover after disruption, and how hosts and microbes sustain communication. These are big questions that requires cross scale and interdisciplinary approaches to address. But by piecing these aspects together, we can better understand how organisms through a holobiont lens.