“Experiments,” observed French physiologist Claude Bernard in An Introduction to the Study of Experimental Medicine (1865), “may be performed on man, but within what limits?” In the nineteenth and twentieth centuries, answers to Bernard’s rhetorical question have differed as physicians, scientists, and soldiers have sought to define the appropriate conduct of human experimentation. Whereas Bernard argued that “The principle of medical and surgical morality consists in never performing on man an experiment which might be harmful to him to any extent, even though the result might be highly advantageous to science,” German and Japanese physicians in the Second World War performed experiments on concentration camp inmates and prisoners that were calculated to maim and kill their subjects. Although the limits of ethical experimentation have wide, and in some cases grotesque, variations, physicians and scientists have never been free to experiment at will and without regard for the welfare of research subjects – animal and human. In Nazi Germany, in a hideous reversal of the usual norms regarding human experimentation, Nazi doctors were able to use concentration camp inmates as experimental subjects without restraint, but they were restricted by law in their use of laboratory animals. Part of this chapter explores the ways in which the practice of human experimentation has been constrained in the last two centuries and the groups – physicians, legislators, activists, and members of the lay public – who have participated in defining and implementing limits on human subject research.