The current accepted model for respiratory rhythm and pattern formation dictates that a medullary inhibitory circuitry is crucial for normal breathing; however this topic is still an area of great contention. We demonstrated that the mechanisms essential for breathing combine both intrinsic cellular properties and dynamic synaptic interactions, with a major emphasis on reciprocal inhibition. With this arrangement, the central pattern generator can produce different modes of oscillatory respiratory behaviour and the circuitries pertaining to each of them can operate independently when disconnected experimentally. This not only confers the robustness and flexibility necessary for operation, but allows network reconfiguration when responding to changes in state (metabolic, arousal) or patho-physiological situations ensuring that ventilation persists. It also implies that failure in inhibitory circuitry would result in rhythm irregularity and central apnoeas. One example is the respiratory pathology featured in patients with Rett Syndrome (RTT), an autism spectrum disorder caused by mutations in the gene that encodes the DNA binding protein methyl-CpG-binding protein 2 (MeCP2). Included in the phenotype are frequent apnoeas, breathing irregularities and periodic breathing. The deficiency in MeCP2 function has been shown to affect synaptic transmission (including GABA) on multiple levels. In a mouse model of Rett syndrome, we found that insufficiency of GABAergic synaptic transmission in discrete brainstem loci was key for generating the RTT respiratory phenotype with important therapeutic implications. More recently, we generated novel viral vectors that allow us to genetically target GABAergic and glycinergic neurones providing further insight into the crucial functional role and connectivity of brainstem inhibitory neurone subpopulations. Using transgenic animals, genetic targeting of respiratory inhibitory neurones and optogenetics, I will demonstrate the essential role of synaptic inhibition within both pontine and ventral medullary respiratory regions in the generation of the eupnoeic breathing pattern.