Overdiagnosis and overtreatment are often thought of as relatively recent phenomena, influenced by a contemporary combination of technology, specialization, payment models, marketing, and supply-related demand. Yet a quick glance at the historical record reveals that physicians and medical manufacturers have been accused of iatrogenic excess for centuries, if not millennia. Medicine has long had therapeutic solutions that search for ever-increasing diagnostic problems. Whether the intervention at hand has been leeches and lancets, calomel and cathartics, aspirins and amphetamines, or statins and SSRIs, medical history is replete with skeptical critiques of diagnostic and therapeutic enthusiasm. The opportunity cost of this profusion shapes the other side of the coin: chronic persistence of underdiagnosis and undertreatment. Drawing from key controversies of the 19th and 20th centuries, we chart the enduring challenges of inter-related diagnostic and therapeutic excess. As the present critique of overdiagnosis and overtreatment seeks to mobilize resources from inside and outside of medicine to rein in these impulses, we provide an instructive historical context from which to act.