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Donor-derived cell-free DNA refers to the cell-free DNA derived from apoptosis or necrosis of allograft tissue, circulating in the body fluids of patients after organ transplantation, and carries health information on the donor tissue. In the past two years, donor-derived cell-free DNA has rapidly become a research hotspot in the field of graft rejection detection after organ transplant. Recent published data have increased our understanding of donor-derived cell-free DNA in the field of kidney transplantation, especially in association with acute rejection. Donor-derived cell-free DNA is predicted to become the next-generation biomarker for the non-invasive detection of allograft rejection. This article reviews the research, involving donor-derived cell-free DNA in ischemia-reperfusion injury, delayed graft function, acute rejection (antibody mediated rejection and T-cell mediated rejection), and BK virus nephropathy. We further discuss the limitations of current research models and suggest directions for future study.