AbstractDuring development and adult life synapses are remodeled in response to genetic programs and environmental cues. This synaptic plasticity is thought to be the basis of learning and memory. The larval neuromuscular junction of Drosophila is established during embryogenesis and grows during larval development to accommodate muscle growth and maintain synaptic homeostasis. This growth is dependent on bidirectional communication between the motoneuron and the muscle fiber. The best‐characterized retrograde signaling pathway is defined by Glass bottom boat (Gbb), a morphogen of the transforming growth factor‐β (TGF‐β) superfamily. Gbb acts as a muscle‐derived retrograde signal that activates the TGF‐β pathway presynaptically. This pathway includes the type II receptor Wishful thinking, type I receptors Thick veins and Saxophone, and the second messenger Smads Mothers against dpp (Mad) and Medea. Mutations that block this pathway result in small synapses that are morphologically aberrant and severely impaired functionally. An emerging anterograde signaling pathway is defined by Wingless, a morphogen of the Wnt family that acts as a motoneuron‐derived anterograde signal required for both pre‐ and postsynaptic development. In the absence of Wingless the neuronal microtubule cytoskeleton regulator Futsch is down‐regulated and synaptic growth impaired. Some of these morphogens have conserved roles in mammalian synaptogenesis, and genetic analysis suggests that additional signaling molecules are required for synaptic growth at the Drosophila neuromuscular junction. © 2005 Wiley Periodicals, Inc. J Neurobiol 64: 417–434, 2005