Maintaining pH homeostasis is vital for all mammalian cells since hydrogen and hydroxyl ions perform important functions in the regulation of metabolism. Today, it is believed that maintaining the pH in the neutral range (pH 7.2–7.6) in the nervous system is necessary for its normal functioning, while small changes in pH affect the excitability of neurons, synaptic transmission, neurotransmitter transport and intercellular communication. Sensitivity to changes in pH is a feature of many membrane proteins that play a key role in neurotransmission. Recent studies have revealed the presence in the nervous system of protein molecules, which are sensors of a significant change in the pH of the extracellular environment in both acidic (to pH 5) and alkaline (to pH 9) areas. It has been established that a change in the pH of the extracellular environment causes various cellular responses in which ion channels, ionotropic receptors, G protein-coupled receptors, connexins and receptor tyrosine kinases are involved. The presence of these proteins in the nervous system suggests that local acid–base balance shifts are one of the key factors regulating neuronal activity. This review describes the properties of neuronal pH-sensitive proteins.