Earth’s deep terrestrial biosphere is home to the majority of prokaryotes — archaea and bacteria — on our planet, yet we have little knowledge on how these microbes interact with each other, with their ecosystem and with potential viruses. In our recently published research, which I summarize in this review, we investigated the interactions of microbes in deep subsurface ecosystems of suboxic and anoxic groundwater aquifers using genome-resolved metagenomics. During our research, we developed a new platform called uBin that enables researchers to curate reconstructed genomes of bacteria and archaea. We used a large database of curated bacterial genomes to deduce that microbial replication linearly declines with ecosystem depth. However, subsurface ecosystems impacted by geological degassing showed a high overall replication index of bacteria. These ecosystems can vary greatly in microbial diversity with a high incidence of bacteria of the Candidate Phyla Radiation, which have little metabolic capacity and are presumably episymbionts or scavengers. Using a combination of metagenomics and metalipidomics, we inferred that these organisms cannot synthesize their own lipids but instead retrieve these essential biomolecules from their surroundings. We also found that organisms of the phylum Altiarchaeota are prevalent in these carbon-dioxide contaminated groundwaters and that their lifestyle is chemolithoautotrophic. Interactions of Altiarchaeota with other biological entities are complex and span episymbionts of the phylum Huberarchaeota as well as hitherto unknown viruses, the lifestyle of which is likely lysogenic. Overall, I conclude that the deep biosphere has great genetic potential that remains to be explored and humanity is just beginning to understand the complexity of life below Earth’s critical zone.