Immunotherapy strategies for cancer are focused on inducing effective and specific cytotoxic responses mediated by CD8 T cells. On the other hand, immunosuppressive mechanisms induced by the tumor, such as the generation of tumor-specific CD4(+)CD25(+)FoxP3(+) Tregs, conspire against the efficacy of immunotherapies. It has been considered that, similar to what has been observed in the context of immunological responses towards microbes, CD4 help is indispensable for the development of a successful and long-lasting (memory) CD8 immune response. In the recent article, Côté et al. reported that, in a mouse model of melanoma, total ablation of CD4 help does not hamper the development of a specific antitumor memory CD8 response. In addition, ablation of CD4 was more successful than strategies to deplete CD25 Tregs in generating memory CD8 T cells. These data opens the door for therapies destined to induce effective antitumor immune responses by ablation of whole CD4 T-cell populations.