Electrophysiological measurements of single synapses are challenging given the size of a single synapse relative to a patch pipette. In addition, one has to take into account the limitations of microscopes in that they need to provide acceptable visualization of a single synapse for patching. However, despite these limitations, researchers have successfully measured single synaptic function along dendrites. The purpose of this chapter is to introduce the techniques that can be implemented to measure single synaptic function. Included in this chapter are such techniques as localized perfusion, localized electrical stimulation, photostimulation, and imaging. These techniques are designed with the assumption that multiple excitatory synapses do not contact a single spine, but rather only one synapse per spine. Whereas this assumption is supported by some empirical data , other data suggest otherwise , meaning that a complete understanding of the anatomical region is necessary before beginning single synapse experiments.