Throughout the developing nervous system of higher vertebrates, synaptic connections are concurrently being established and eliminated. The consequence of this synaptic remodeling is that axons strengthen their connections with some targets while completely disconnecting from other postsynaptic cells. The transition from multiple to single axonal innervation of skeletal muscle fibers is the most accessible example of this developmental reorganization. In muscle, the elimination of axonal input appears to be driven by a protracted competition between different axons co-innervating the same junction, with the muscle fiber as intermediary. Asynchronous synaptic activity may be the factor that differentiates the competing inputs. In some circumstances, synapses can also be lost in ways that are independent of activity. Similarities between activity-dependent and activity-independent synapse elimination provide insights into mechanisms underlying developmental synaptic reorganization.