In this paper, we review experimental evidence for a novel form of persistent synaptic plasticity we call metaplasticity. Metaplasticity is induced by synaptic or cellular activity, but it is not necessarily expressed as a change in the efficacy of normal synaptic transmission. Instead, it is manifest as a change in the ability to induce subsequent synaptic plasticity, such as long-term potentiation or depression. Thus, metaplasticity is a higher-order form of synaptic plasticity. Metaplasticity might involve alterations in NMDA-receptor function in some cases, but there are many other candidate mechanisms. The induction of metaplasticity complicates the interpretation of many commonly studied aspects of synaptic plasticity, such as saturation and biochemical correlates.