The field of transfusion medicine has evolved rapidly in recent years, but the central principle of transfusion is still simple, namely, the antigen-antibody interaction. Daratumumab (DARA), a monoclonal antibody (MoAb), was developed to treat relapsed/refractory multiple myeloma (RRMM). DARA works by targeting the CD38 portion of malignant cells; however, this drug attaches to the red blood cell (RBC) reagents used in blood banks, further complicating the antibody identification work-up. The AABB (formerly known as the American Association of Blood Banks) has issued a memorandum on how blood banks can effectively address panreactivity caused by DARA. Dithiothreitol (DTT), a common reagent in blood banks, has emerged as an inexpensive and practical way to dissolve panreactivity caused by DARA. However, DTT is known to destroy the Kell antigen blood group and other, less frequently encountered blood group antigens. Other promising alternative solutions, such as umbilical cord RBCs, screening cells, and neutralization, are not widely available yet. The exploration of these issues and options, in this review of the literature, is intended to guide blood bank technologists in dealing with panagglutination reactivity caused by DARA.