Native nephrectomy (NN) is not routinely performed in the context of kidney transplantation. Certain clinical circumstances necessitate performing NN such as large polycystic kidneys impairing patient’s quality of life and hindering graft implantation. NN may be done either before, simultaneously with, or after kidney transplantation. Although several studies have reported the potential benefits of the pretransplantation approach, others defended the simultaneous approach postulating that it is feasible and satisfactory. Nevertheless, still the ideal timing of NN is not settled, and several factors determine the choice of nephrectomy timing, including the presence of pressure symptoms, residual diuresis, and adequate space for the graft and living (not deceased) kidney donation. Answering these questions will help in decision making to attain an individualized approach that would help in achieving optimum timing of NN in relation to kidney transplantation.