Synapse proteomics has recently resulted in a quantum leap in knowledge of the protein composition of brain synapses and its phosphorylation. We now have the first draft picture of the synapse, comprising approximately 1000 proteins. This is not matched by available methods of functional analysis either in reduced systems or in whole animals. Fewer than 20% of synapse proteome proteins have a known function in the nervous system. A concerted effort is required to establish new technical approaches before we can understand the diversity of functions conferred by the synapse proteome on the synapse, the neuron and the animal. This review will highlight this change in knowledge and discuss current technical and interpretative limitations challenged by synapse proteomics.