KIR-ligand mismatch in the graft-versus-host (GVH) direction between donor and recipient in allogeneic stem cell transplantation (ASCT) may trigger NK cell alloreactivity. Such KIR-ligand mismatch has been associated with improved survival after haploidentical ASCT for acute myeloid leukemia (AML). Its role in unrelated ASCT has been more controversial. In an analysis of 190 unrelated ASCTs for hematological malignancies, we observed that KIR-ligand mismatch was associated with increased transplantation related mortality (TRM) and decreased overall survival. The increased TRM was a consequence of a higher rate of infections. Thus, the presence of alloreactive NK cells can potentially interfere with effective immunity to infections in the early post-transplantation period. Here, we review the discrepancies in published reports on KIR-ligand mismatch in unrelated ASCT.