It is a central principle in medical ethics that vulnerable patients are entitled to a degree of protection that reflects their vulnerability. In critical care research, this protection is often established by means of so-called proxy consent. Proxy consent for research participation constitutes a substituted judgement by a close relative or friend, based on knowledge of patient's values, preferences, and view of life. For the consent to be genuine, the proxy must be informed of and understand three fundamental aspects of research practice: (1) that participation is voluntary and the consent can be withdrawn at any time; (2) that the research is designed to benefit future patients and society as a whole, and not the individual study participant; and (3) that participation involves an incremental non-therapeutic risk. If this is not fulfilled because the research is to be conducted under circumstances where the proxy is unavailable, adequate protection of the patient must be ensured by other means. Thus, the research must be designed specifically to benefit critically ill patients, and the incremental non-therapeutic risk must only comprise a minimal risk.