CD4(+) T cells are central to the function of the immune system but their role in tumor immunity remains underappreciated. It is becoming clear that there is an enormous diversity of CD4(+) T cell polarization patterns including Th1, Th2, Th17, and regulatory T cells (Tregs). These functionally divergent T cell subsets can have opposing effects -- they can trigger tumor rejection or inhibit treatment after adoptive cell transfer. Some polarized CD4(+) cells have plasticity, and their phenotypes and functions can evolve in vivo. Recent advances in understanding of polarization and differentiation of lymphocytes, as well as some intriguing developments in the clinic, indicate that the use of CD4(+) T cell subsets in the immunotherapy of cancer has unrealized potential.