Synaptic modification of transmission is a general phenomenon expressed at almost every excitatory synapse in the mammalian brain. Over the last three decades, much has been discovered about the cellular, synaptic, molecular, and signaling mechanisms responsible for controlling synaptic transmission and plasticity. Here, we present a brief review of these mechanisms with emphasis on the current understanding of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA-R) trafficking and Ras-mitogen-activated protein kinase (MAPK) signaling events involved in controlling synaptic transmission.