During the last decade, increased understanding of the molecular mechanisms responsible for immune activation to protect against challenges by tumor cells has revolutionized the field of immunotherapy research. It has been demonstrated that the dysfunction of the host's immune system represents one of the major mechanisms by which tumors evade immunosurveillance. This is due, for example, to T cell anergy, the existence of regulatory T cells, and systemic defects of dendritic cells derived from tumor patients. In addition, escape from immunosurveillance can also be linked to tumor-related factors, including secretion of immunosuppressive cytokines, resistance to apoptosis, and deficient expression of immunomodulatory molecules and major histocompatibility complex (MHC) class I antigens possibly due to immunoselection. Both host- and tumor-related mechanisms can lead to a failure to mount a proper anti-tumor-specific immune response, and these are frequently key factors in limiting the success of cancer immunotherapy.