Natural killer cells play an important role in innate immunity. They act against infected and transformed cells as part of the immune surveillance process. Their interactions with the human leukocyte antigens (HLAs) create a situation where they may act against donor hematopoietic cells following stem cell transplantation. Both killer immunoglobulin-like receptors (KIRs) and HLA types of donor and recipient are relevant in the generation of graft-vs-leukemia or graft-vs-host reactions. This chapter reviews the current knowledge on the involvement of natural killer cells in the events following hematopoietic stem cell transplantation, the structure of the genetic complex encoding the KIRs and provides a PCR-based genotyping scheme for KIR genes.