Cancer immunology and immunotherapy are driving forces of research and development in oncology, mostly focusing on CD8 ⁺ T cells and the tumor microenvironment. Recent progress highlights the importance of CD4 ⁺ T cells, corresponding to the long-known fact that CD4 ⁺ T cells are central players and coordinators of innate and antigen-specific immune responses. Moreover, they have now been recognized as anti-tumor effector cells in their own right. Here we review the current status of CD4 ⁺ T cells in cancer, which hold great promise for improving knowledge and therapies in cancer.