The bases for an efficient anti-tumor immune response begin to be better defined. Nonetheless, neoplastic cells develop various strategies to escape immune surveillance, which are discussed here in order to better design the therapeutic possibilities of immune manipulation. The absence of specific tumor antigen as well as the weak expression of major histocompatibility complex (MHC) molecules hinder the recognition of the neoplastic cells by T lymphocytes. The defect of expression by the tumor of the ligands for the T cell activation costimulatory molecules is particularly harmful for the immune response since it induces tolerance. Finally, tumor cells can inactivate effector T lymphocytes through the secretion of inhibitory cytokines, induction of apoptosis or functional inactivation. The multiplicity of the means to oppose an effective anti-tumor response challenges the adaptative mechanisms of the immune system. For example, the natural killer cells target tumor cells not expressing MHC class I molecules. Numerous possibilities of tumor immunogenicity restoration have been demonstrated at least in vitro, such as stimulation of the cancerous cells by CD40 or cytokine treatment, which could lead to several promising therapeutical approaches.