Four decades ago, several health movements were sprouting in isolation. In 1980, the environmental group Friends of the Earth expanded the World Health Organization definition of health, reminding citizenry that, “health is a state of complete physical, mental, social and ecological well-being and not merely the absence of disease—personal health involves planetary health”. At the same time, a small group of medical clinicians were voicing the concept of “clinical ecology”—that is, a perspective that sees illness, especially chronic illness, as a response to the total lived experience and the surroundings in which “exposures” accumulate. In parallel, other groups advanced the concept of holistic medicine. In 1977, the progressive physician-scientist Jonas Salk stated that “we are entering into a new Epoch in which holistic medicine will be the dominant model”. However, only recently have the primary messages of these mostly isolated movements merged into a unified interdisciplinary discourse. The grand, interconnected challenges of our time—an epidemic of non-communicable diseases, global socioeconomic inequalities, biodiversity losses, climate change, disconnect from the natural environment—demands that all of medicine be viewed from an ecological perspective. Aided by advances in ‘omics’ technology, it is increasingly clear that each person maintains complex, biologically-relevant microbial ecosystems, and those ecosystems are, in turn, a product of the lived experiences within larger social, political, and economic ecosystems. Recognizing that 21st-century medicine is, in fact, clinical ecology can help clear an additional path as we attempt to exit the Anthropocene.