Throughout the brain, postsynaptic neurons release substances from their cell bodies and dendrites that regulate the strength of the synapses they receive. Diverse chemical messengers have been implicated in retrograde signaling from postsynaptic neurons to presynaptic boutons. Here, we provide an overview of the signaling systems that lead to rapid changes in synaptic strength. We consider the capabilities, specializations, and physiological roles of each type of signaling system.