Episodic memories are formed in the mammalian hippocampus but retained there only for a few weeks, compared to the months and years of memory storage provided in the neocortex. Mark Schnitzer and colleagues have used a new microendoscopic method to reveal that hippocampal dendritic spines in the CA1 region undergo complete turnover in less than six weeks in mice, in contrast to the much greater stability of synapses in the neocortex. This work illustrates a possible physical basis for the transience of hippocampal memory processes.