Long-term depression (LTD) displayed in the cerebellar cortex is a persistent decrease of the transmission efficacy from granule cell to Purkinje cells. LTD is induced when two inputs to a Purkinje cell, one from a climbing fiber and the other from a set of granule cell axons, are repeatedly associated. This article defines the physiological characteristics of LTD and reviews recent findings of complex signal transduction processes, which underlie LTD, involving a variety of substances that eventually lead to the inactivation of ionotropic glutamate receptors. Evidence also indicates that climbing fibers convey error signals, not only for an error consequent to a movement but also for errors arising from control mechanisms in the central nervous system. LTD is thus thought to play a key role in reorganization of the neuronal network of the cerebellum by depressing those granule cell–Purkinje cell synapses that are activated in association with errors. This view has been supported by showing that pharmacological or genetic inhibition of LTD impairs various forms of motor learning.