The energy metabolism of the adult human brain almost completely depends on glucose. The functional coupling of regional cerebral blood flow and local cerebral glucose metabolism has been established in a wide range of experiments using autoradiographic techniques in rats, cats, and monkeys as well as double-tracer techniques in humans. Glucose utilization in turn reflects neuronal activity and more specifically synaptic, mainly presynaptic, activity. The majority of glucose is needed for the maintenance of membrane potentials and restoration of ion gradients. PET as well as fMRI may be used to study changes in blood flow or flow-related phenomena in human subjects in vivo. Both techniques monitor changes of synaptic activity in a population of cells. These changes may be due to excitation or inhibition. More than 85% of cerebral glucose is used by neurons (mainly presynaptic axon terminals), while the remainder may at least partly account for metabolic processes in glial cells. Monitoring of regional cerebral blood flow with PET or fMRI thus mainly reflects neuronal and more specifically (pre-) synaptic activity.