Neuroblastoma (NB) is a common neuroectodermal tumor of childhood with low response to conventional therapy in patients with advanced stage disease. Among novel strategies, immumotherapy has attracted much interest. However, scanty information is available about the immunogenicity of human NB. Here, we review our data showing that human NB may evade the control mediated by T cytotoxic lymphocytes and natural killer (NK) cells through multiple mechanisms: (i) downregulation of HLA class I molecules and antigen processing machinery components (ii) downregulation of activating ligands for the activating immunoreceptor NKG2D expressed by cytotoxic T lymphocytes and NK cells. Additional mechanisms of immune evasion used by human NB cells are discussed.