Predicting humoral alloimmune potential in transplant recipients is the objective of histocompatibility testing and depends upon accurate donor typing and sensitive and specific testing for antibodies to human leukocyte antigen. This review for the transplant clinician will describe the evolution and current practices of histocompatibility testing methods for typing, crossmatching and antibody screening. Novel methods of measuring T-cell alloimmune potential will also be briefly discussed. Emphasis is given to the clinical applicability and limitations of each test, and the collective consideration of all tests in concert, as part of the immunologic risk assessment of the solid organ transplant recipient.