Fast inhibitory synaptic inhibition is critical for shaping the functional properties of neuronal networks. At a receptor level, synaptic inhibition is mediated by type A g-aminobutyric acid receptors (GABAARs), which are primarily permeable to chloride (Cl-) ions. Therefore, together with the neuronal membrane potential, the transmembrane gradient for Cl- sets the driving force for Cl-flux across these receptors, controlling the properties of inhibitory signaling. In this talk I will 1) explore what establishes the driving force for Cl- in neurons, 2) how the transmembrane Cl- gradient can change during activity and how this alters the input-output properties of neurons and 3) how Cl- dynamics are important for our understanding and treatment of epileptic seizures.