Kidney transplantation has been the optimal treatment for end-stage kidney disease for almost 70 years, with increasing frequency over this period. Despite the prevalence of the procedure, allograft rejection continues to impact transplant recipients, with consequences ranging from hospitalization to allograft failure. Rates of rejection have declined over time, which has been largely attributed to developments in immunosuppressive therapy, understanding of the immune system, and monitoring. Developments in these therapies, as well as an improved understanding of rejection risk and the epidemiology of rejection, are dependent on a foundational understanding of the pathophysiology of rejection. This review explains the interconnected mechanisms behind antibody-mediated and T-cell-mediated rejection and highlights how these processes contribute to outcomes and can inform future progress.