Retrograde signaling from the postsynaptic cell to the presynaptic neuron is essential for the development, maintenance, and activity-dependent modification of synaptic connections. This review covers various forms of retrograde interactions at developing and mature synapses. First, we discuss evidence for early retrograde inductive events during synaptogenesis and how maturation of presynaptic structure and function is affected by signals from the postsynaptic cell. Second, we review the evidence that retrograde interactions are involved in activity-dependent synapse competition and elimination in developing nervous systems and in long-term potentiation and depression at mature synapses. Third, we review evidence for various forms of retrograde signaling via membrane-permeant factors, secreted factors, and membrane-bound factors. Finally, we discuss the evidence and physiological implications of the long-range propagation of retrograde signals to the cell body and other parts of the presynaptic neuron.