Informed consent has become a sine qua non for the ethical conduct of human subjects research, with few exceptions. Indeed, so taken for granted is the notion that investigators must obtain subjects’ consent before proceeding with research that it is difficult for most investigators and research staff to imagine that human subjects research was ever conducted in any other way. An examination of the history of informed consent to research, however, reveals that it is largely a creation of the second half of the twentieth century and has never been without controversy. Moreover, a careful examination of informed consent as actually applied in research settings reveals a highly imperfect process, much in need of adjustment. Thus, the future of informed consent to research is by no means clear.