The neuromuscular junction (NMJ) represents the most well studied synapse and is widely regarded as structurally and functionally less complicated than neuronal synapses in the brain. Recent studies, however, have identified the localization and function of new signaling molecules at the NMJ. Surprisingly, many synaptic proteins previously identified in the brain are indeed also concentrated on the postsynaptic muscle side of the NMJ. These include the serine/threonine kinase Cdk5, the neurotrophin receptor TrkB, Eph receptors and ephrins, NMDA receptors and nitric oxide synthase, various PDZ-domain scaffold proteins, and beta-amyloid precursor protein. These observations indicate that the molecular composition of NMJ is much more intricate than we originally thought. The potential significance of these new signaling molecules at the NMJ will be discussed.