Precise neural circuitry is established and maintained through a regulated balance of synapse stabilization and disassembly. Currently, little is known about the molecular mechanisms that specify synapse stability versus disassembly.Here, we demonstrate that presynaptic spectrin is an essential scaffold that is required to maintain synapse stability at the Drosophila neuromuscular junction (NMJ). Loss of presynaptic spectrin leads to synapse disassembly and ultimately to the elimination of the NMJ. Synapse elimination is documented through light-level, ultrastructural, and electrophysiological assays. These combined assays reveal that impaired neurotransmission is secondary to synapse retraction. We demonstrate that loss of presynaptic, but not postsynaptic, spectrin leads to the disorganization and elimination of essential synaptic cell-adhesion molecules. In addition, we provide evidence of altered axonal transport and disrupted synaptic microtubules as events that contribute to synapse retraction in animals lacking presynaptic spectrin.Our data suggest that presynaptic spectrin functions as an essential presynaptic scaffold that may link synaptic cell adhesion with the stabilization of the underlying microtubule cytoskeleton.