Leukocyte Ig-like receptors (LILRs)/Ig-like transcripts (ILTs) are expressed on innate and adaptive immune cells and maintain immune homeostasis. LILRs consist of activating and inhibitory-type receptors that regulate adequate cellular functions. LILRs were firstly identified as MHC class I receptors, therefore expression and/or polymorphisms of LILRs are reported to associate with autoimmune disorders and transplant rejection; however, recent accumulating evidences have revealed that LILRs recognize with diverse ligands including bacteria and virus. In addition, inhibitory LILRB2 (ILT4) and murine relative paired Ig-like receptor (PIR)-B are expressed on neuron and is involved in the dysregulation of central nervous system via interaction with neuronal ligands including amyloid β-protein. In this review, we summarize recent discoveries on the functions of inhibitory MHC class I receptors, and discuss their regulatory roles in immune responses and neural functions.