The number of highly sensitized patients on the transplant waiting list continues to rise. HLA allosensitization has profound effects on the wait time to transplant, rejection rates, and long-term outcomes. While technological advances with high sensitivity and specificity have facilitated the detection of donor specific antibodies, there is no consensus on diagnostic and prognostic values of these tests. Recently, multiple desensitization protocols have been developed that comprise high dose IVIG, low dose IVIG with plasmapheresis, rituximab and more novel agents including Bortezomib. Although these preconditioning protocols have led to successful transplantation of sensitized patients, long-term outcomes are limited and suboptimal. Randomized clinical trials are needed to determine optimal treatment and monitoring strategies in patients that are highly sensitized across the HLA barrier.