This article discusses the role of surrogate decision-makers for persons who are cognitively impaired and cannot give informed consent. Questions raised follow. Is surrogate consent in research analogous to proxy consent in health care? What are some issues in surrogate consent? How does the risk–benefit ratio affect the consent process? What are the investigator's responsibilities regarding surrogate consent? Issues discussed include advance directives, durable power of attorney, legally authorized representatives, substituted judgment, double informed consent, responsibilities of surrogates, and barriers to informed consent. The article ends with recommendations to clarify state and national laws, change research designs, and establish a national mechanism for reviewing promising research that is usually prohibited.