Endophytes are isolated from every plant species investigated to date, so the metabolome coevolution has been affecting the plants’ (microbiota) ethnobotanic, especially therapeutic, usage. Asteraceae fulfill the rationale for plant selection to isolate endophytes since most of the species of this family have a long tradition of healing usage, confirmed by modern pharmacognosy. The present review compiles recent references on the endophyte−Asteraceae spp. interactions, targeting the secondary metabolites profile as created by both members of this biological system. Endophyte fungi associated with Asteraceae have been collected globally, however, dominant taxa that produce bioactive compounds were specific for the plant populations of different geographic origins. Endophytic fungi richness within the host plant and the biological activity were positively associated. Moreover, the pharmacological action was linked to the plant part, so differential forms of biological interactions in roots, stem, leaves, inflorescences were developed between endophytic fungi and host plants. The comparative analysis of the Asteraceae host and/or fungal endophyte therapeutic activity showed similarities that need a future explanation on the metabolome level.