The influence of humans on ecosystem dynamics has been, and continues to be, profound. Anthropogenic effects are expected to amplify as human populations continue to increase. Concern over these effects has given rise to a large number of studies focusing on impacts of human activities on individual species or on biotic community structure and composition. Lacking are studies on interactions, particularly mutualisms. Because of the role of mutualisms in ecosystem stability, such studies are critically needed if we are to begin to better understand and predict the responses of ecosystems to anthropogenic change. Most organisms are involved in at least one mutualism, and many in several. Mutualisms facilitate the ability of partners to exploit particular habitats and resources, and play a large role in determining ecological boundaries. When change disrupts, enhances, or introduces new organisms into a mutualism, the outcome and stability of the original partnership(s) is altered as are effects of the symbiosis on the community and ecosystem as a whole. In this paper, using examples from six microbe-insect mutualisms in forest and savanna settings, we showcase how varied and complex the responses of mutualisms can be to an equally varied set of anthropogenic influences. We also show how alterations of mutualisms may ramify throughout affected systems. We stress that researchers must be cognizant that many observed changes in the behaviors, abundances, and distributions of organisms due to human activities are likely to be mediated by mutualists which may alter predictions and actual outcomes in significant ways.