Effective function of the locomotor system in the Drosophila larva requires a continuous adjustment of synaptic architecture and neurotransmission at the neuromuscular junction (NMJ). This feature has made the larval NMJ a favorite model to study the genetic and molecular mechanisms underlying synapse plasticity. This chapter will review experimental strategies used to study plasticity at the NMJ, the cellular parameters affected during plastic changes, and many of the known molecules involved in plastic changes. In addition, signal transduction pathways activated during plasticity will be discussed.