American ginseng (Panax quinquefolius L.) is an uncommon to rare understory plant of the eastern deciduous forest. Harvesting to supply the Asian traditional medicine market made ginseng North America's most harvested wild plant for two centuries, eventually prompting a listing on CITES Appendix II. The prominence of this representative understory plant has led to its use as a phytometer to better understand how environmental changes are affecting many lesser-known species that constitute the diverse temperate flora of eastern North America. We review recent scientific findings concerning this remarkable phytometer species, identifying factors through its history of direct and indirect interactions with humans that have led to the current condition of the species. Harvest, deer browse, and climate change effects have been studied in detail, and all represent unique interacting threats to ginseng's long-term persistence. Finally, we synthesize our current understanding by portraying ginseng's existence in thousands of small populations, precariously poised to either escape or be drawn further toward extinction by the actions of our own species.