Postsynaptic membrane rafts (or lipid rafts) (PSRs), together with the postsynaptic density (PSD), are believed to be major sites important for postsynaptic signaling, function, and plasticity. Although the PSD has received much attention and is extensively investigated, PSR roles and their relationship with PSDs are poorly understood. Our recent work has identified PSD–PSR complexes from synaptic membranes of the rat brain and demonstrated specific interactions between them in vitro. Here, we review recent progress in this field, focusing on the molecular identities of the PSR, its biochemical purification, and its potential roles in postsynaptic signaling, function, and plasticity via cross talk with the PSD. We propose that the PSR and PSD are two major postsynaptic signaling domains that interact physiologically, and that PSRs are indispensable to PSD functions. Roles of PSRs in synaptogenesis, growth, and maturation of developing PSDs, and support and regulation of functions and plasticity of mature PSDs are discussed.