Despite long-standing critiques of the conduct of underpowered clinical trials, the practice not only remains widespread, but also has garnered increasing support. Patients and healthy volunteers continue to participate in research that may be of limited clinical value, and authors recently have offered 2 related arguments to support the validity and value of underpowered clinical trials: that meta-analysis may "save" small studies by providing a means to combine the results with those of other similar studies to enable estimates of an intervention's efficacy, and that although small studies may not provide a good basis for testing hypotheses, they may provide valuable estimates of treatment effects using confidence intervals. In this article, we examine these arguments in light of the distinctive moral issues associated with the conduct of underpowered trials, the disclosures that are owed to potential participants in underpowered trials so they may make autonomous enrollment decisions, and the circumstances in which the prospects for future meta-analyses may justify individually underpowered trials. We conclude that underpowered trials are ethical in only 2 situations: small trials of interventions for rare diseases in which investigators document explicit plans for including their results with those of similar trials in a prospective meta-analysis, and early-phase trials in the development of drugs or devices, provided they are adequately powered for defined purposes other than randomized treatment comparisons. In both cases, investigators must inform prospective subjects that their participation may only indirectly contribute to future health care benefits.