When a blackbird swallows an earthworm, there is little doubt about the nature of the interaction. Sadly, few microbial interactions are this clear. This is particularly true when bacteria reside inside eukaryotes. Who gains, who loses, and the role of evolution are large questions in the biology of microbial interactions. Many look at the mechanisms of interaction, but here we take a different approach. First we explore the landscape of interactions across the eastern US, determining how commonly specific bacteria interact with amoebae, beginning with the obligate endosymbionts Amoebophilis and Neoclamydia and the eukaryote host Dictyostelium discoideum. We image the interactions and measure health effects on the host. Then we turn to a novel facultative endosymbiont, Paraburkholderia spp. where geographic distribution and health effects can be measured for both host and endosymbiont. We name three new species, two of which are highly dependent on the host and then use experimental evolution techniques to reveal how tightly they have co-evolved. Combining the tools of landscape surveys, microscopy, fitness assays, genomics, and experimental evolution allow a much deeper understanding of host-pathogen or host-mutualist interactions.