This chapter examines the history of human experimentation in psychiatry, with a concentration on developments in the 20th century. It explores bodily therapies that developed out of a desire to harness biological evidence to support physical interventions that might provide relief from mental symptoms. We show that some of these experiments helped to set the stage for another phase of experimentation characterized by drug trials, which introduced new methodological terminology and concepts. Double blind trials, randomization, controlled trial methodology, and the interrogation of placebo effects changed the way that psychiatric experimentation unfolded in the second half of the 20th century. Our chapter shows that the new language of clinical trials created new moments of scientific optimism, and also generated unprecedented commercial opportunities. Despite the differences between clinical drug trials and physical interventions of the somatic era, the history psychiatry reveals a legacy of experimentation aimed at diagnosing, classifying, and treating mental disorders. Although approaches, theories, and methods have changed, experimentation has remained a central part of the field. By considering how historians and scholars have interpreted this past, we chart a longer relationship between experimentation and therapy that has characterized different moments of psychiatric history as well as galvanized responses against psychiatry for wielding undue power over people with mental illness.