Established tumors are complex masses that contain not only neoplastic cells but also nontransformed cellular elements such as stromal cells, the neovasculature, and the full gamut of immune cells. However, evidence suggests that, unlike cells found in lymphoid organs that productively respond to acute infections, immune cells in tumors are dysregulated and functionally impaired. Tumor masses can contain regulatory lymphocytes, myeloid-derived suppressor cells, alternatively activated macrophages, and dendritic cells. Ablation or reprogramming of this aberrant microenvironment might dramatically augment cancer therapies, and this strategy is currently being deployed in a variety of clinical trials. A better understanding of the cellular constituents of tumors and the mechanisms involved in immune evasion may help guide the next generation of innovative cancer immunotherapies.