Live kidney donor transplantation across immunological barriers, either blood group or positive crossmatch [ABO- and human leucocyte antigens (HLA)-incompatible kidney transplantation, respectively], is now practised widely across many transplant centres. This provides transplantation opportunities to patients that hitherto would have been deemed contra-indicated and would subsequently have waited indefinitely for a suitably matched kidney. Protocols have evolved with time as experience has grown and now a variety of desensitization strategies are currently practised to overcome such immunological barriers. In addition, desensitization protocols are complemented by kidney paired donation exchange schemes and therefore incompatible patients now have strategies to either confront or bypass immunological barriers, respectively. As the field expands it is clear that non-transplant clinicians will be exposed to incompatible kidney transplant recipients outside of experienced centres. It is therefore timely to review the evolution of practice that have led to current desensitization modalities, contrast protocols and outcomes of current regimens and speculate on future direction of incompatible kidney transplantation.