This paper gives an overview of the placebo effect in popular culture, especially as it pertains to the work of authors Patrick O'Brian and Sinclair Lewis. The beloved physician as placebo, and the clinician scientist as villain are themes that respectively inform the novels, The Hundred Days and Arrowsmith. Excerpts from the novels, and from film show how the placebo effect, and the randomized clinical trial, have emerged into popular culture, and evolved over time.