Cancer takes advantage of the ability to hide from the immune system by exploiting a series of immune escape mechanisms. Among these mechanisms are the hijackings of immune cell-intrinsic checkpoints that are induced on T-cell activation. Blockade of these checkpoints–cytotoxic T-lymphocyte-associated antigen 4 or the programmed death 1 receptor–recently provided the first evidence of activity of an immune-modulation approach in the treatment of solid tumors. The future frontier in the immunotherapeutics of breast cancer requires identification of predictive factors. The immune system remembers what it targets, so once the system is correctly activated, it may mediate a long-lasting tumor response.