Patients with advanced cancer are heterogenous not only with respect to the underlying histology and biology of their cancer, but also in other important ways. Advanced cancer patients also vary with respect to their overall health status, their preferences, the local extent of their underlying disease, the number of sites of their metastatic spread, the overall bulk of their cancer, and their sources of suffering. One of the most important decisions that must be made in caring for these patients is determining the role of anticancer therapy in the comprehensive plan of care. This important decision has implications regarding the number and type of health providers involved in the care, the proper setting for the delivery of care, the third-party and out-of-pocket costs of care, the level of family support necessary to implement the care properly, and the overall trajectory of care. This chapter will address the use of systemic anticancer therapy for advanced cancer patients with a focus on five major questions: (1) Is there a conceptual framework that can be used to inform this decision? (2) What is the range of possible specific goals for this therapy? (3) What are the most useful predictors of response to therapy? (4) What are the broad categories of therapies that are commonly used? (5) How are patients followed once therapy is started?