A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K+ homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K+ channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K+ channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer. This Commentary discusses Eil’s finding in the context of the central role that K+ channels play in the suppressed state of TILs as they mediate the immunosuppressive effects of multiple conditions of the TME including hypoxia and adenosine.