Evidence indicates that the healthy immune system is necessary for control of malignant disease and that immune suppression associated with cancer contributes to its progression. Tumors have developed strategies to successfully evade the host immune system, and various molecular and cellular mechanisms responsible for tumor evasion have been identified. Certain of these mechanisms target immune anti-tumor effector cells. Dysfunction and apoptosis of these cells in the tumor-bearing host creates an immune imbalance that cannot be corrected by immunotherapies aimed only at activation of anti-tumor immune responses. Reversal of existing immune dysfunction(s) and normalization of lymphocyte homeostasis in patients with cancer needs to be a part of future cancer immunotherapy. Therapeutic strategies are being designed to correct the immune imbalance, deliver adequate in vivo stimulation, transfer effector T cells capable of in vivo expansion and provide protection for the immune effector cells re-populating the host. Survival of these cells and long-term memory development in patients with malignancy are necessary for improving clinical benefits of cancer immunotherapies.