It is increasingly recognized that cancer does not involve only formation of a tumor, but also systemic changes in the host. Alterations in number, spatial relationship, and function of immune cells have been identified in cancer patients' blood, lymph nodes, spleen, and bone marrow. Importantly, these changes correlate with clinical outcome, demonstrating that systemic effects may persist in some patients after initial therapy that underlie future relapse. In this chapter, we will review these recent findings on the systemic effects of cancer.