The last decade has witnessed a significant turn in our understanding of the mechanisms responsible for the decline of cognitive functions in aged brain. As has been demonstrated by detailed morphological reassessments, the senescence-related changes in cognition cannot be attributed to a simple decrease in the number of neurons. It is becoming clearer that a major cause of age-induced deterioration of brain capability involves much subtler changes at the level of synapses. These changes are either morphological, i.e. reduction in the number of effective synapses and/or functional alterations, i.e. changes in the efficacy of remaining synapses. Important questions are now raised regarding the mechanisms which mediate these synaptic changes. Clearly, an important candidate is calcium, the cytotoxic role of which is already firmly established. The wealth of evidence collected so far regarding the changes of Ca2+ homeostasis in aged neurons shows that the overall duration of cytoplasmic Ca2+ signals becomes longer. This is the most consistent result, demonstrated on different preparations and using different techniques. What is not yet clear is the underlying mechanism, as this result could be explained either through an increased Ca2+ influx or because of a deficit in the Ca2+ buffering/clearance systems. It is conceivable that these prolonged Ca2+ signals may exert a local excitotoxic effect, removing preferentially the most active synapses. Uncovering of the role of Ca2+ in the synaptic function of the aged brain presents an exciting challenge for all those involved in the neurobiology of the senescent CNS.