To address the question of what value is added by assessing quality of life (QOL) in symptom management trials in cancer, we used the model of Wilson and Cleary to identify what is measured by the most commonly used QOL instruments. Examples of clinical trials are presented demonstrating the contributions of these broad-based QOL instruments in terms of symptoms, functioning, general health perceptions, and overall QOL. The examples show that QOL instruments can provide valuable information about side effects and impact on other aspects of life, which would not be captured by a more narrowly focused measure of the target symptom. A better understanding is needed of the differences in what QOL instruments measure, since conclusions regarding the effectiveness of treatment may differ depending on which one is used to assess outcomes. Head-to-head comparisons of instruments within the same studies would increase precision for selecting QOL instruments for symptom management trials.