Legumes have the almost unique ability to establish symbiotic associations with rhizobia and arbuscular mycorrhizal fungi. Forward and reverse genetics have identified a large number of genes that are required for either or both interactions. However, and in sharp contrast to natural soils, these interactions have been almost exclusively investigated under laboratory conditions by using separate inoculation systems, whereas both symbionts are simultaneously present in the field. Considering our recent understanding of the individual symbioses, the community is now promisingly positioned to co-inoculate plants with two or more microbes in order to understand mechanistically how legumes efficiently balance, regulate and potentially separate these symbioses and other endophytic microbes within the same root. Here, we discuss a number of key control layers that should be considered when assessing tri- or multipartite beneficial interactions and that may contribute to colonization patterns in legume roots.