In synaptic signaling, the response of an individual neuron is determined by its complement of receptors. As discussed in other chapters in this volume, ligand‐gated ion channels mediate fast synaptic transmission between neurons. However, signaling within an individual neuron is mediated by a complex set of interactions that occur primarily as a result of G protein linked signal transduction. The beauty of this system is in its diversity and inherent capacity for amplification and plasticity in the modulation of many different cellular functions. The initial signal sequence in this type of signaling typically is the generation of a second messenger inside the cell that then in turn activates a number of different proteins capable of modifying cellular processes. This chapter will present examples and an in depth discussion of these intracellular signaling pathways beginning with G protein linked signaling, perpetuated by G protein coupled receptor (GPCR) stimulation. Next, ion channel modulation via G proteins as well as direct GPCR interactions with the channels will be discussed. The long list of intracellular downstream effector pathways including cyclic nucleotide signaling, protein kinase signaling and calcium regulated signaling are also described. The final focus of the chapter is protein phosphorylation cascades, a predominant mechanism in many signal transduction schemes. It is through these complex interactions that an individual cell is able to respond to neurotransmitter stimulation and modify many of its cellular processes to contribute to the overall symphony of synaptic signaling.