Foundation species are species that create and define particular ecosystems; control in large measure the distribution and abundance of associated flora and fauna; and modulate core ecosystem processes, such as energy flux and biogeochemical cycles. However, whether a particular species plays a foundational role in a system is not simply asserted. Rather, it is a hypothesis to be tested, and such tests are best done with large-scale, long-term manipulative experiments. The utility of such experiments is illustrated through a review of the Harvard Forest Hemlock Removal Experiment (HF-HeRE), a multidecadal, multihectare experiment designed to test the foundational role of eastern hemlock, Tsuga canadensis, in eastern North American forests. Experimental removal of T. canadensis has revealed that after 10 years, this species has pronounced, long-term effects on associated flora and fauna, but shorter-term effects on energy flux and nutrient cycles. We hypothesize that on century-long scales, slower changes in soil microbial associates will further alter ecosystem processes in T. canadensis stands. HF-HeRE may indeed continue for >100 years, but at such time scales, episodic disturbances and changes in regional climate and land cover can be expected to interact in novel ways with these forests and their foundation species.