The cellular processes that govern neuronal function are highly complex, with many basic cell biological pathways uniquely adapted to perform the elaborate information processing achieved by the brain. This is particularly evident in the trafficking and regulation of membrane proteins to and from synapses, which can be a long distance away from the cell body and number in the thousands. The regulation of neurotransmitter receptors, such as the AMPA-type glutamate receptors (AMPARs), the major excitatory neurotransmitter receptors in the brain, is a crucial mechanism for the modulation of synaptic transmission. The levels of AMPARs at synapses are very dynamic, and it is these plastic changes in synaptic function that are thought to underlie information storage in the brain. Thus, understanding the cellular machinery that controls AMPAR trafficking will be critical for understanding the cellular basis of behavior as well as many neurological diseases. Here we describe the life cycle of AMPARs, from their biogenesis, through their journey to the synapse, and ultimately through their demise, and discuss how the modulation of this process is essential for brain function.