Protein synthesis in dendrites is essential for long-lasting synaptic plasticity, but little is known about how synaptic activity is coupled to mRNA translation. Using hippocampal neuron cultures and slices, we have investigated the role of glutamate receptors and mTOR signaling in control of dendritic protein synthesis. We find: 1) Specific antagonists of NMDA, AMPA and metabotropic glutamate receptors abolish glutamate-induced dendritic protein synthesis, whereas agonists of NMDA and metabotropic but not AMPA glutamate receptors activate protein synthesis in dendrites; 2) Inhibition of mTOR signaling, as well as its upstream activators, PI3K and AKT, block NMDA receptor-dependent dendritic protein synthesis. Conversely, activation of mTOR signaling induces dendritic protein synthesis; and 3) Dendritic protein synthesis activated by tetanus-mediated LTP induction in hippocampal slices requires NMDA receptors and mTOR signaling. These results suggest critical role of the NMDA receptor-mTOR signaling pathway in regulating protein synthesis in dendrites of hippocampal neurons.