Fifty years after Beecher’s landmark article, an old question is being debated anew: is it ethical to conduct clinical research without consent? This paper provides a systematic analysis of this question. First, it describes five clinical trials that have either been conducted (or proposed) without the subjects providing consent. Second, it reviews a number of conditions that are often provided to justify bypassing of consent and finds that only some of them qualify as necessary conditions for bypassing consent. When those conditions are applied to the clinical trials, only one trial without consent (a type of cluster randomized trial) appears clearly justified; bypassing consent in the remaining four trials is more questionable. The present analysis may be useful in the interpretation of the current U.S. regulations that provide for waivers and alterations of informed consent.