Patients with advanced cancer face difficult decisions regarding their treatment, and many will need to make difficult choices about end-of-life care because although cancer-directed therapies are increasingly available, few provide a cure. High-quality cancer care includes access to palliative care throughout the cancer care continuum, and increasing evidence suggests that timely enrollment in hospice can increase quality of life for patients dying from cancer. Therefore, clinicians must learn to recognize patients who are hospice-eligible and to develop prognostication and communication skills that enable honest provider-patient dialogue about end-of-life options. In this article, the authors review available tools for prognostication in advanced cancer and present a method for discussing prognosis by using the SPIKES acronym. In addition, by using patient-identified goals and service needs, the authors recommend a method for making a hospice referral after disclosure of poor prognosis. CA Cancer J Clin 2009;59:250-263. ? 2009 American Cancer Society, Inc.