Refinement of synaptic connections during development requires both the elimination of some inputs and the strengthening of others. It is well accepted that this competitive process takes place throughout the nervous system and relies on synaptic activity. However, the mechanisms that link activity to refinement remain largely unresolved. Here we demonstrate that refinement of preganglionic axons in sympathetic ganglia, a process that depends unequivocally on synaptic activity, involves eukaryotic initiation factor 4E binding protein (4E-BP), a protein that regulates cap-dependent translation. In mice lacking the 3 nicotinic receptor subunit, silent synapses between preganglionic axons and postsynaptic nicotinic neurons do not refine unless synaptic activity is restored, or surprisingly, when 4E-BP is absent. Our findings demonstrate that synapses can refine in the absence of synaptic activity during development and identify 4E-BP as a critical player in this process.