The idea that all members of a society have a duty to help promote scientific and medical advances has been the subject of debate, 1 and it has recently been suggested that patients should be able to participate in ‘‘research that may be beyond the bounds of current clinical research practice’’ and that ‘‘even when greater-than-usual risks may be present, such research can be both ethically and scientifically justified.’’ 2 This is partly based on the argument that all of us are obliged to participate in research and that where there is ‘‘some reasonable likelihood [of] a beneficial effect’’ it is appropriate for ‘‘‘risky’ research’’ to proceed. 3 Here I do not dispute this contention but draw attention to some of the issues that are raised by involving those with no other hope in experimental procedures. These are important because of the position—desperately ill with no alternatives—such patients are in. The UK’s Nuffield Council on Bioethics has recognized that medical progress has sometimes been made at the ‘‘expense’’ of those who first received a new procedure, and that ‘‘[i]n some cases, it has been cruel to offer a possible life-saving procedure that resulted in a long drawn-out painful death, instead of a relatively peaceful end. The offer of such a procedure in itself puts pressure on patients to accept—and may distort judgement.’’ 4 I am not arguing that there should be a blanket ban on involving those with no other hope in experimental procedures; rather, I argue that, if they are to be involved, then they must be legally protected and that the use of such procedures is scientifically justified and ethically reviewed. In this article I examine international and national ethical and professional guidance on offering experimental procedures to those with no other hope and explore the common law on experimental procedures in England and Wales. The issues highlighted here are not jurisdiction specific; rather, the regulatory framework in England and Wales is used as a lens through which to explore and highlight the protection offered to those with no other hope. In so doing I question whether the existing regulatory structures appropriately protect those with no other hope and draw on ethical guidance from New Zealand that suggests ways to proceed. Care must be taken with involving such patients in experimental procedures because they may be particularly vulnerable and open to exploitation, even if this is not the deliberate or conscious aim of those seeking to perform the procedure for the first time. Despite this risk, selection issues in this context have rarely been considered. This may be because their involvement has been assumed This article is dedicated to Professor David Price, who was an inspirational and supportive academic, colleague, and mentor.