John F. MacDonald was a close friend and mentor whose life was ended far too soon on April 22, 2014. To those who knew him, John was an endearing blend of fiery Scotsman, compassionate socialist, dedicated family man, and tireless investigator. Those close to him valued his loyalty and friendship, relished his biting wit, and puzzled at his self-deprecating manner. His career spanned a remarkable period of discovery from the early identification of excitatory amino acid, to the molecular cloning and characterization of glutamate receptors and the elucidation of mechanisms responsible for regulating their function. A true pioneer in each of these areas, John’s research has had a lasting impact on our understanding of excitatory synaptic transmission and its plasticity. Our intent in commemorating John’s work is to focus on some notable discoveries that highlight the impact and innovative aspects of John’s work. In doing so, we also wish to highlight just how greatly our understanding of the glutamate transmitter systems has advanced since the late 1970s, when John first launched his independent neuroscience career.