Abstract TRP channels were first identified as membrane proteins mediating phototransduction in fruit flies. Astrocytes were initially referred to as the silent elements of the nervous system. At the time these discoveries were made, few would have suspected TRP channels and astrocytes could contribute significantly to our understanding of brain signalling. Recent findings, however, put TRP channels and astrocytes in the spotlight, describe their ability to modulate the activity of specific sets of synapses, and raise some interesting questions. What makes astrocytes capable of exerting cell-specific effects on interneuronal signals? How do different synapses respond to changes in astrocytic function and in the local micro-structure of the neuropil? Can astrocytes be considered good candidate targets for therapeutic intervention to treat neurological diseases? Here I discuss the recent developments on TRP channels and astrocytes that have made us aware of the many structural and functional features of synapses that still need to be discovered and that could lead a new avant-garde in decoding the cellular and molecular basis of brain (dys)function.