Ligand- or antibody-mediated aggregation of surface receptors, such as antigen receptors on T cells, B cells and mast cells, induces signaling pathways resulting in diverse functional responses. Cell activation can also be initiated by aggregation of glycoproteins anchored to the plasma membrane via glycosylphosphatidylinositol (GPI), as well as by some glycolipids. Numerous recent data suggest that the signaling capacity of the aggregated membrane glycoconjugates reflects their association with specialized membrane microdomains (lipid rafts), enriched in glycosphingolipids, cholesterol and signal transduction molecules. These domains are relatively resistant to solubilization by nonionic detergents at low temperature, and due to their low density they can be easily isolated by density gradient ultracentrifugation. Under certain conditions the lipid rafts can be observed by microscopy. Although the concept of lipid rafts as hot spots of transmembrane signaling (signalosomes) is an attractive hypothesis, the issue is controversial and little is known about their properties and functions under in vivo conditions. This minireview is focused on recent research on the role of lipid rafts in transmembrane signaling, based mostly on biochemical, morphological and functional studies of mast cells and their derivatives.