Some critics question whether research on complementary and alternative modalities for patients with cancer can be done efficiently in traditional clinical settings. This article reviews a program of complementary medicine research that has been done in a traditional clinical setting over the past 30 years. Trials using complementary therapies for both symptom management and cancer treatment done by the Mayo Clinic and the North Central Cancer Treatment Group are reviewed. Twenty-seven studies have been developed using complementary therapies, addressing such issues as mucosal and epidermal toxicity, hot flashes, lymphedema, anorexia and cachexia, insomnia, cognitive dysfunction, fatigue, and cancer treatment. Nineteen of them have been completed and have had results published in peer-reviewed clinical journals, whereas two manuscripts are in press. Two other trials have recently completed accrual, and the data are being analyzed so that manuscripts can be prepared. In addition, four clinical trials are actively accruing patients. The data presented in this article demonstrate that complementary and alternative medicine research can be done in a scientifically sound manner. Well-designed and adequately powered studies can be implemented, and large numbers of patients can be accrued. The resulting research evaluations can be published in peer-reviewed medical journals.