alpha-Amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors mediate most fast excitatory synaptic transmission in the mammalian CNS. They play a central role in synapse stabilisation and plasticity and their prolonged activation is potently neurotoxic. Developmental and activity-dependent changes in the functional synaptic expression of these receptors are subject to tight cellular regulation. The molecular and cellular mechanisms which control the postsynaptic insertion and arrangement of individual AMPA receptor variants are therefore the subject of intense investigation and in the last two years there has been significant progress towards elucidating some of the processes involved. Much of the new information has come from the application of the yeast two-hybrid assay, which has led to the discovery of a hitherto unexpected complexity of proteins which selectively interact with individual AMPA receptor subunits. These proteins have been implicated in the regulation of AMPA receptor post-translational modification, targeting and trafficking, surface expression and anchoring. The aim of this article is to present an overview of the major interacting proteins described so far and to place these in the context of how they may participate in the well ordered series of events controlling the cell biology of AMPA receptors.