This paper traces the development of health-related Quality of Life instruments over the last half century. It identifies the emergence of key components of quality of life measurement in other health status questionnaires between about 1950 and 1980 and their formalization in Quality of Life instruments in the mid 1980s. The common developmental thread that linked these Quality of Life instruments and their precursors was the identification of 'distal symptoms' that represented the impact of illness beyond its immediate bodily manifestations. The measurement of distal symptoms through Quality of Life instruments also served to detach symptoms from their customary patho-physiological referent. Other contemporary examples of these free-floating symptoms reinforce the argument that the nature and meaning of symptoms has been transformed over recent decades.