Exchange donor programs and desensitization protocols are available options for ABO-incompatible and positive cross-match living donor kidney transplantations. Patient and donor blood types, the degree of sensitization, and DSA titers should be considered to achieve successful kidney transplantation in recipients with incompatible living donors. Highly sensitized blood type O patients with ABO-incompatible living donors, or highly sensitized patients with a positive cross-match (with low DSA titer) to their AB donors should be considered for a desensitization protocol as a first priority. Narrowly sensitized patients with a positive cross-match (and high DSA titer) should be considered for an exchange donor program if possible. Patients with positive cross-match O donors can be easily matched and benefit from an exchange program. Exchange donor programs and desensitization protocols are complementary strategies to overcome HLA and ABO antibody barriers.