BACKGROUND: In recent years, there has been a growing recognition that improvements in quality of life may be as important as improvements in quantity of life in patients with advanced cancer. With this goal in mind, many oncology trials now seek to evaluate palliative endpoints as well as disease progression and survival. METHODS: Methodologic advances and challenges in evaluating palliative endpoints in oncology clinical trials are reviewed. RESULTS: Valid and reliable self-report measures have been developed that permit evaluation of palliative endpoints. Issues to consider in conducting research on palliative endpoints include the selection of appropriate outcome measures, the number and timing of outcome assessments, and the handling of missing data. CONCLUSIONS: The inclusion of palliative endpoints into clinical trials in oncology has the potential to advance clinical care by identifying chemotherapeutic agents that are effective in improving the quality of life of patients with advanced cancer.