Before an organ transplant is performed, donor-recipient compatibility must be established by a crossmatch in much the same way as it is done for blood transfusions. The target antigens in organ transplantation, however, are HLA rather than blood group molecules, and the target cells are lymphocytes instead of red cells. If antidonor antibodies are detected, it is important to know whether they are IgG or IgM, whether they recognize T and/or B cells, and whether the antibody reactivity is weak or strong. These test requirements are better met by flow cytometry than by the standard cytotoxicity technique. A growing body of evidence now indicates that flow cytometry can provide more sensitive and timely crossmatch information than cytotoxicity assays to decide whether or not a transplant should be done. Flow cytometry crossmatch (FCXM) is a new and evolving technique that has already been found to be extremely useful in the clinical transplantation setting, even though significant questions yet remain about the precision and reliability of using flow cytometry to quantify alloantibodies and about the limits of normal reactivity in the assay. This article reviews important technical details of the FCXM and its interpretation and clinical application in transplantation medicine.