In this episode, we explore the science and clinical importance of crossmatching in abdominal organ transplantation—focusing on kidney and liver grafts. We delve into the key differences between T cell and B cell crossmatches, examining the roles of complement-dependent cytotoxicity (CDC) and flow cytometry in detecting donor-specific antibodies (DSAs). While a positive T cell crossmatch—particularly in kidney transplantation—often signifies a prohibitive immunologic risk due to class I HLA antibodies and hyperacute rejection, B cell crossmatches reveal subtler threats like class II DSAs. We contrast the high-stakes sensitivity of crossmatching in kidney transplantation with the liver’s immunological tolerance, where even positive crossmatches may not preclude successful transplantation. Emerging innovations such as virtual crossmatching, C1q binding assays, and epitope-level matching are also discussed, highlighting a future where transplant immunology becomes ever more precise and personalized.