Ever since their first description in neurons, dendritic spines could be visualized only in fixed tissue, using high-power light and electron microscopy. Recent studies have been able to measure the free intracellular Ca2+ concentration ([Ca2+]i) in dendritic spines of live neurons, and the results suggest that the spine is an independent cellular Ca2+ compartment. Other recent observations have indicated that the density of spines on dendrites changes in a dynamic fashion depending on ongoing neuronal activity. Together, these findings have led to the proposal that the dendritic spine is not only a storage device for long-term memory but perhaps a means for isolating the cell from the harmful consequences of synaptically evoked surges in [Ca2+]i. In other words, the dendritic spine is a neuroprotectant. This hypothesis has specific testable implications, including relating cell activity to spine density.