The purpose of the present chapter is to review in broad outline the older concepts of denaturation of proteins, to contrast them with the interpretations developed more recently (using selected but not isolated examples) and to suggest a re-orientation in our attitude to this class of changes in the properties of proteins. Because the survey is extensive rather than intensive, omission of particular items of experimental work from detailed consideration is not to be interpreted as an adverse reflection upon them. Individual studies have been selected from the period 1952-June, 1963 because they illustrate (or contrast with) the broad currents of recent work. Investigations of isolated, specialized problems have been purposely omitted.