Retrograde signals influence neuronal survival, differentiation, synaptogenesis, and plasticity. Several recent papers describe novel roles for the well-studied TGF-β pathway in retrograde synaptic signaling. While each dissects spatial and molecular aspects of TGF-β signaling in a specific synaptic context, together these studies demonstrate that a specific retrograde signal may be interpreted in diverse, neuron-specific ways. Thus, a neuron's intrinsic properties and its other extrinsic signaling inputs determine its cellular and genomic response to TGF-β.