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The graft-versus-tumor (GvT) effect refers to the phenomenon whereby transplanted immune cells, primarily from a donor graft, selectively attack and eliminate tumor cells in a recipient host. This effect is most commonly observed in the context of allogeneic hematopoietic stem cell transplantation (HSCT), particularly for patients with hematological malignancies like leukemia or lymphoma. During the transplantation process, the donor's immune cells, particularly T cells, recognize the recipient's tumor cells as foreign due to differences in human leukocyte antigen (HLA) expressions. As a result, these donor T cells mount an immune response against the tumor, leading to a substantial reduction or even complete eradication of the cancer. The GvT effect is intricately linked to the concept of graft-versus-host disease (GvHD), where the donor immune cells also attack normal host tissues, creating a delicate balance between leveraging the immune response to combat cancer and minimizing damage to healthy cells. Notably, the GvT effect can often be enhanced by using immunomodulatory drugs or strategies that increase the activity of T cells post-transplant. Researchers have identified various mechanisms by which the GvT effect operates, including the direct killing of tumor cells by cytotoxic T lymphocytes (CTLs) and the release of pro-inflammatory cytokines that can further activate and attract additional immune cells to the tumor site. While the GvT effect is a powerful tool in the fight against tumors, it does come with significant challenges. The risk of acute and chronic GvHD can lead to considerable morbidity and impact quality of life. Consequently, there is ongoing research aimed at understanding the optimal conditions under which the GvT effect can be maximally harnessed while controlling the adverse effects of GvHD. This includes exploring potential ways to selectively enhance T cell responses against tumor antigens while sparing normal tissues, thus providing a more targeted approach to cancer immunotherapy. Furthermore, advancements in cell therapy, such as the development of CAR T-cell therapies, also hold promise for enhancing the GvT effect by equipping T cells with specific recognition capabilities for tumor-associated antigens. In essence, the GvT effect represents a critical mechanism of immune-mediated tumor rejection in the context of allogeneic transplantation, highlighting the potential of the immune system to not only recognize but also effectively suppress malignancies. As the field of cancer treatment continues to evolve, understanding and refining the GvT effect remains paramount to improving outcomes for patients undergoing transplantation for cancer, paving the way for more effective and less toxic therapeutic strategies.