In this article important areas of health-related quality of life (HRQL) research and major achievements are described, illustrated by studies conducted with cancer patients. Some of the challenges facing this line of research are elucidated. The areas of HRQL research described are distinguished according to their intended objective, including research aimed to assess treatment outcome and/or to qualify rates of survival, to assess late problems, to predict mortality, and to support information-giving. It was found that HRQL assessments are useful in clinical trials and cost-effectiveness studies and that they point to areas where former cancer patients may experience serious problems. It was also found that HRQL data are strong predictors of survival. Finally, HRQL assessments were found to stimulate doctor-patient communication. Three challenges are discussed, including the use of proxy respondents, the need to take response shift into account, and the interpretation of HRQL results as clinically meaningful. New research areas, such as HRQL related to genetic testing and as experienced by ethnic minorities urgently need to be taken on.