Host-associated bacteria are found across the tree of life. In this opinion article, we propose that population genetics theory can be used to probe the conditions that form the path toward such symbioses. We illustrate how mutation-selection models generate insights into the maintenance of a symbiont under transmission between generations and from the environment. We outline how basic features of host population size and life history shape the fixation of a heritable symbiont in a host population, suggesting elevated fixation probabilities in long-lived hosts. Finally, whenever the fitness effects of the symbiont vary over time, reduced efficiency of selection increases the fixation of a deleterious symbiont. Our predictions of the properties of hosts, symbionts, and their ecological contexts that impact symbiont establishment frame expectations across systems.