The human leukocyte Ig-like receptor family is part of the paired receptor system. The receptors are widely expressed by various immune cells, and new functions continue to emerge. Understanding the range of functions of the receptors is of general interest because several types of pathogens exploit the receptors and genetic diversity of the receptors has been linked to various autoimmune diseases. Class I major histocompatibility molecules were the first ligands appreciated for these receptors, but the types of ligands identified over the last several years are quite diverse, including intact pathogens, immune-modulatory proteins, and molecules normally found within the CNS. This review focuses on the types of ligands described to date, how the individual receptors bind to several distinct types of ligands, and the known functional consequences of those interactions.