The genes encoding the killer immunoglobulin-like receptors (KIR) are situated within a segment of DNA that has undergone expansion and contraction over time due in large part to unequal crossing over. Consequently, individuals exhibit considerable haplotypic variation in terms of gene content. The highly polymorphic human leukocyte antigen (HLA) class I loci encode ligands for the KIR; thus, it is not surprising that KIR genes also show significant allelic polymorphism. As a result of the receptor-ligand relationship between KIR and HLA, functionally relevant KIR–HLA combinations need to be considered in the analysis of these genes as they relate to disease outcomes. This chapter will describe a genotyping method for identifying the presence/absence of the KIR genes and general approaches to data analysis in disease association studies.