The human MHC class I genes, HLA-E, -F and -G are referred to as non-classical or class Ib genes and are distinguished from their close relatives (the classical HLA class I genes) by expression patterns and low allelic polymorphism. To date, most studies that relate these molecules to the immunology of pregnancy have concerned only HLA-G. However, recent advances have suggested potential unique roles as well for HLA-E and HLA-F in pregnancy. A notable advance was the observation that all three proteins are expressed on the surface of extravillous trophoblast that has invaded the maternal decidua. Given this expression site, possibly the only cell type in human development where this occurs, it is logical to hypothesize that all three antigens, each with its own unique receptor-ligand interaction(s), contribute collectively to enable the growth of the developing child. In this review, we examine and discuss the accumulated data on expression and function of HLA-E and HLA-F and attempt to relate what is known to the involvement of HLA-E and -F in human pregnancy.