The contribution of retrograde signaling to information processing in the brain has been contemplated for a long time, especially with respect to central nervous system development and long-term synaptic plasticity. During the past few years, however, the concept of retrograde signaling has been expanding to include short-term modifications of synaptic efficacy. The classic point of view on synaptic transmission represents it as a unidirectional transfer of information from presynaptic to postsynaptic sites. This paradigm has, however, been questioned in several experimental studies of neurons in different brain regions. These results suggest that a fast retrograde signal, which provides feedback, exists in active synaptic contacts. In particular, it was found that the dendritic release of retrograde messengers controls the efficacy of synaptic transmission in both excitatory and inhibitory connections between neocortical pyramidal cells and interneurons. The present review discusses these findings and the mechanisms underlying synaptic retrograde signaling.