Recent genomic analysis has shown that proteins with immunoglobulin superfamily (IgSF) domains are extremely abundant and their number has increased markedly in evolution correlating with the development of the adaptive immune system. The IgSF domain is particularly good at being recognised and is involved in many different kinds of interactions. Thus, analysis of the properties of these domains can act as a paradigm for thinking about the roles of newly identified gene products. This review summarises the identification, function and properties of IgSF domains including, their size, variety of interactions, their strength of binding, role of glycosylation and organisation with other proteins.