There is not yet sufficient evidence-based experience for the coordinated treatment of three symptoms that cluster in cancer: pain, depression, and fatigue. Each symptom taken individually has accepted treatment modalities. With some overlap between these symptoms, established treatments for one symptom may "cross-over" and reduce the burden of one, or both of the others. To optimize patient care in advance of the evidence basis, attention to these symptoms is value-added for patients and their families. Standardized screening using the Distress Thermometer for physical, practical, emotional, or spiritual symptoms helps effectively identify patients whose symptoms warrant attention. Cancer Supportive Services, an innovative program at the Continuum Cancer Centers of New York at Beth Israel and St. Luke's-Roosevelt, provides comprehensive intervention throughout the trajectory of care for pain, depression, and fatigue. These services are provided in tandem with efforts to cure or contain the cancer. Cancer Supportive Services sets up a natural entry point to survivors' follow-up or end-of-life care. Such an effort reinforces a basic principle that active symptom management is integral to each patient encounter in the cancer treatment setting.