The tetraspanins are a superfamily of membrane glycoproteins which facilitate the interaction of membrane and intracellular signalling molecules (e.g., integrins, pro-growth factors and their receptors, protein kinase-C) in the formation of membrane signalling microdomains (sometimes referred to as the tetraspanin web). A proximal localisation/association of tetraspanins with Fc receptors (FcR) has been implied by the repeated rediscoveries of tetraspanins as the targets of antibodies which activate platelets and other blood cells through co-ligation of FcR. Direct evidence of tetraspanin-FcR interactions has come from immunoprecipitation and co-immunofluorescence studies. The functional effects of this interaction remain unclear, but tetraspanins have been identified as negative regulators of FcR signalling independently of co-ligation, indicating potential roles in modulating FcR function in co-ordination with the activity of other signalling/adhesion molecules in the tetraspanin web. Given their capacity to influence FcR signalling, tetraspanins could provide specific therapeutic targets for immune disorders including rheumatoid arthritis, asthma and allergies.