Several studies have shown that neurons in the central and peripheral nervous systems express a variety of chemokine receptors (CKRs). Activation of these receptors can influence neuronal signaling by regulating synaptic transmission and neuronal excitability. This article presents electrophysiological methods that are currently used to study the normal and pathophysiological role for CKRs in the nervous system. Conventional electrophysiological methods such as patch-clamp recording of isolated neurons, brain slices, and heterologous expression systems are described. In addition, single-cell reverse transcription-polymerase chain reaction is discussed as a technique that can be used in conjunction with patch-clamp recording to further investigate the molecular basis of neuronal CKR activation.