Synaptic plasticity is an important cellular mechanism for the formation of memory in neuronal circuits of the brain. Research during the past two decades has revealed surprisingly complex signal-transduction processes that underlie various forms of synaptic plasticity. More than 30 molecules are involved in the induction of long-term depression (LTD) — a unique form of synaptic plasticity in the cerebellum. Here, I review recent data on these molecules, defining their roles as mediators or modulators, coincidence detectors or components of a self-regenerating circuit, and show how they are organized to form an efficient molecular machinery for LTD induction.