Pain management is an integral component of comprehensive cancer care. Designing an effective pain control strategy for the individual patient requires knowledge of the ways in which a patient's cancer, cancer therapy, and pain therapy can interact. Two important aspects of cancer that affect the way in which pain is managed are the cancer's treatability and components of its pathophysiology that themselves do not cause pain (the cancer's "nonpain" pathophysiology). Cancer treatability modifies the need for pain management and the appropriateness of invasive pain procedures. Cancer nonpain pathophysiology can interfere with the oral administration of medications, narrow the patient's therapeutic window for analgesic drugs, limit the effectiveness of psychologic pain therapies, and complicate or preclude invasive pain-relieving procedures. In addition, cancer therapy can interfere with or enhance pain therapy and vice versa. Cancer therapy can interfere with pain therapy by causing pain or by producing other adverse effects. Cancer therapy can enhance pain therapy by reducing the extent of cancer, by acting as a coanalgesic, and by providing intravenous access for parenteral drug administration to patients who require it. Pain therapy can interfere with cancer therapy by increasing or complicating the adverse effects of cancer therapy. Pain therapy can enhance cancer therapy by improving patient performance, and certain palliative surgical procedures may have the ancillary effect of improving organ function. Five case descriptions are presented as illustrations of effective integration of pain management into comprehensive cancer care.