The anticytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody ipilimumab was approved recently by the U.S. Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma. Anti-CTLA-4 treatment yields tumor responses or stable disease that may last months or years. Antitumor responses can occur within the first few weeks or even months after initiation of treatment, even as the disease appears to be progressing or new lesions are detected. Most side effects are immune related, consistent with the immune-based mechanism of action, and generally manageable with supportive measures and steroids. With anti-CTLA-4 therapy, patient response differs (both clinically and psychologically) to that generally observed with chemotherapy or other agents used to treat advanced cancer. Patients and caregivers require education about the likely patterns of response to treatment to help them understand why beneficial clinical outcomes may require weeks or months to occur and why continued treatment may be advisable, even when the disease may appear to be progressing. At the author's institution, the staff have noted that patients also need increased psychological support as a result of these clinical features and decisions. Patients and caregivers require instruction on recognition of potential side effects, the importance of reporting them in a timely manner, and their management.