The proposed involvement of free intracellular calcium concentration ([Ca]i) in neuronal plasticity is examined. While it is generally believed that a rise of [Ca]i is necessary for the triggering of long-term modification of synaptic connections, there are many unresolved issues related to this dogma; it is not entirely clear what is the source of the elevated calcium, how much of a calcium rise is sufficient to produce the synaptic potentiation, where and for how long, and what are the relevant chemical consequences of the transient rise of [Ca]i. It is generally believed that the dendritic spine is the locus of synaptic modification, yet little evidence exists to support this view. High resolution calcium imaging studies may contribute to the clarification of some key issues in the field of neuronal plasticity.