Kidney transplantation is considered the treatment of choice for most individuals with end-stage kidney disease, as well as the most cost-effective renal replacement therapy for the health care system that serves them. Immunologic sensitization, defined by the presence of antibodies directed against foreign HLA (or so called, donor specific antibodies, or DSA), is a significant barrier to kidney transplantation. Further, the presence of DSA is associated with an increase in the incidence of antibody-mediated rejection and decreased graft survival following transplantation. Therapeutic plasma exchange, an extracorporeal therapy directed at removing plasma proteins, including DSA, has proven to be an important part of a comprehensive strategy to minimize the effect of sensitization before, and following kidney transplantation. As such, it offers the promise of increasing access to transplantation, as well as improving outcomes following transplantation. In this concise narrative review, we describe more specifically the benefits of kidney transplantation, the epidemiology of kidney transplantation in the United States, the clinical significance of anti-HLA antibodies, and the evidence supporting a role for therapeutic plasma exchange before and after kidney transplantation.