Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A(1) receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A(2A), A(3), neuropeptide Y, and purinergic P2Y(1) receptors will be described in the first part. The second part deals with interactions between A(1)Rs and ionotropic receptors, especially GABA(A), NMDA, and P2X receptors as well as ATP-sensitive K(+) channels. Finally, the review will discuss new approaches towards treating neurological disorders.