The history of the placebo phenomenon is both interesting and informative. The placebo effect is a core component of health care, and if one considers a contemporary view of placebo effects, this has likely been the case for as long as records exist. An exploration of placebos and placebo effects across several centuries demonstrates many interesting facts, ranging from very early writings and experiments to the modern investigation of placebo mechanisms. A longitudinal review reveals the many challenges that have been faced, whether this is understanding what a placebo is, why it may work, and the meaning of such responses for routine clinical practice. At the core of this process are the concepts surrounding placebo, as these are imperative in the application of placebo to both routine clinical care and in the context of clinical trial design. This narrative review will look at the history of placebo, particularly key aspects over time, with a view to presenting a modern re-conceptualization of this field so as to facilitate ongoing scientific inquiry and to improve health care.