Following the classical work on presynaptic inhibition in the spinal cord, recent work has revealed an astonishing abundance and diversity of presynaptic ionotropic GABA receptors. While modern techniques allow for detailed studies at the cellular and molecular level in almost all regions of the CNS, our understanding of the function of such receptors is still far from complete. One major shortcoming is the lack of knowledge regarding chloride concentration inside axons or axon terminals. Therefore, the voltage change upon activation of presynaptic GABA receptors is difficult to predict. Moreover, even if the presynaptic potential transient was known, it turns out difficult to predict the effects on presynaptic function, which may be differentially influenced by various mechanisms, including activation or inactivation of voltage-gated ion channels and shunt effects. This review summarizes several key examples of presynaptic ionotropic GABA receptors and outlines the possible mechanisms that have to be kept in mind when unravelling this potentially important mechanism of synaptic signalling and plasticity.