How different factors contribute to determine the time course of the basic element of fast glutamate-mediated excitatory postsynaptic currents (mEPSCs) in the central nervous system has been a focus of interest of neurobiologists for some years. In spite of intensive investigations, these mechanisms are not well understood. In this review, basic hypotheses are summarized, and a new hypothesis is proposed, which holds that desensitization of AMPA receptros plays a major role in shaping the time course of fast mEPSCs. According to the new hypothesis, desensitization shortens the time course of mEPSCs largely by reducing the buffering of glutamate molecules by AMPA receptors. The hypothesis accounts for numerous findings on fast mEPSCs and is expected to be equally fruitful as a framework for further experimental and theoretical investigations.