Current data indicates that anti-tumor T cell-mediated immunity correlates with a better prognosis in cancer patients. However, it has widely been demonstrated that tumor cells negatively manage immune attack by activating several immune-suppressive mechanisms. It is, therefore, essential to fully understand how lymphocytes are activated in a tumor microenvironment and, above all, how to prevent these cells from becoming dysfunctional. Tumors produce galectins-1, -3, -7, -8, and -9 as one of the major molecular mechanisms to evade immune control of tumor development. These galectins impact different steps in the establishment of the anti-tumor immune responses. Here, we carry out a critical dissection on the mechanisms through which tumor-derived galectins can influence the production and the functionality of anti-tumor T lymphocytes. This knowledge may help us design more effective immunotherapies to treat human cancers.