Clinical investigations of adoptive therapy in solid tumors have primarily focused on CD8+ cells. A study by Hunder et al. is the first to demonstrate the significance of antigen-specific CD4+ T cells. An in vitro method was used to treat a patient with metastatic melanoma using autologous CD4+ cells against NY-ESO-1 (cancer and/or testis antigen 1). The successful adoptive transfer of antigen-specific CD4+ cells to a patient with metastatic melanoma is not only an important technical accomplishment but also provides increased understanding of tumor immunity. This report demonstrates an impressive persistence of adoptively transferred cells together with durability of clinical response. CD4+ T cells that target a particular antigen can augment T-cell responses to other tumor-associated targets. These observations underline the importance of ongoing research for effective, non-toxic immune therapies for cancer.