Preclinical animal studies convincingly demonstrate that tumor immunity to self-antigens can be actively induced and can translate into effective anti-tumor responses. Among the most challenging of clinical targets for cancer immunotherapy is Tumor Associated Carbohydrate Antigens (TACA). The molecular characterization of TACA suggest that these glycans are both altered and self-antigens. A new appreciation of the interaction of glycans with immune effector cells that will benefit immunotherapy strategies is emerging as more information on the nature of molecular interactions of glycan recognition molecules is obtained. Carbohydrate recognition affects more or less every aspect of the innate and adaptive immune response and their role in immunotherapy of cancer should be considered beyond the existing paradigm of traditional TACA based-vaccines.