Immunologic sensitization, defined by the presence of antibodies directed against donor human leukocyte antigen (or so called donor-specific antibodies [DSA]), is common among those awaiting kidney transplantation, and is associated with worse outcomes following transplant. Existing DSA have historically been screened for pretransplant using complement-dependent cytotoxic crossmatching and their risk circumnavigated through policies that prohibit transplants between incompatible donor–recipient pairs. This risk avoidance strategy maximizes outcomes following transplant, but at the expense of limiting access to transplant for sensitized individuals. Over the last decade, the field of kidney transplantation has moved to actively modify the risks posed by DSA, rather than to simply avoid them. More sensitive detection methods have provided detailed immunologic risk stratification of potential donor–recipient pairs. Desensitization protocols, in which therapeutic aphaeresis plays a central role, have been used to reduce the potential harms posed by DSA. More recently, desensitization and paired donor exchange programs have been used in combination to expand transplantation to highly sensitized patients with incompatible living donors. It is likely that this combination of risk mitigation and avoidance strategies will be used together more often to both maximize individuals’ access to transplant, and optimize patient and graft outcomes.