Quality of life (QL) assessment is now regarded as desirable, if not mandatory, by agencies supporting cancer clinical trials around the world, yet doubts persist about the relevance of QL data to clinical practice. A plethora of QL measures is available but the quality of published work remains suboptimal. The appropriate choice of instrument is essential if outcome measures are to be valid and clinically meaningful. This paper reviews the considerations which should determine the choice of QL questionnaire and, taking the specific example of the EORTC approach, aims to provide users with an update on the current state of the art in the development of cancer-specific QL questionnaires.