In this essay, classical events and related characters in the developments of clinical trial methodology were searched and summarized. The 'first' and major methodological progresses in the milestone events of clinical trials were therefore presented. This study is purposed to delineate the historically vicissitudinous progress of the clinical trial with typical figures and events, study and analyze the profound background of the renovation of clinical research methods, and provide references for clinical and scientific researchers, health policy makers and medical students to comprehensively review the history of clinical trial.