During the past 2 decades, there have been advances in the definition, measurement, and application in clinical trials and practice of health-related quality of life (HRQOL). In addition, the importance of bringing the patient's voice to medical decision making has been increasing. However, there remains some question as to the importance of the HRQOL construct in cancer treatment. This article addresses several issues related to HRQOL in oncology including (1) reasons for including HRQOL measurements in treatment studies, (2) the importance of HRQOL information in the absence of clinical therapeutic benefit, (3) determining clinical significance of HRQOL data, and (4) when it may not be important to measure HRQOL. HRQOL information can be a useful outcome of therapeutic benefit for patients undergoing cancer treatments, especially when it is associated with a clinical intervention such as additional supportive services, symptom management, and a new medicine that reduces tumor size or extends life. Moreover, it is important to establish the meaningful important difference levels on HRQOL questionnaires to trigger health professionals to begin, maintain, or end cancer interventions.