Appelbaum and colleagues first described the “therapeutic misconception” in 1982. There has been much discussion since then about whether and why some patients who enter clinical trials confuse research with treatment and overestimate the nature or likelihood of benefit to them from research in which they enroll, and about whether investigators share in or contribute to any misunderstanding. The therapeutic misconception has been examined empirically in surveys and interviews, some of which focus on phase I trials, and in one published examination of consent forms for phase I oncology research. Thus, Appelbaum and colleagues’ original focus on whether research subjects understood how study design elements like randomization and placebo arms could affect them has expanded to encompass factors characteristic of early-phase trials, such as translation from laboratory and animal studies to human trials and the implications of dose escalation design. However, there has been relatively little discussion of these and other ethical and design questions raised by early-phase clinical research.