Formation of the neuromuscular junction requires a series of reciprocal inductive interactions between the motor neuron and the muscle cell that culminate in the precise juxtaposition of a highly specialized presynaptic nerve terminal with a complex postsynaptic endplate on the muscle surface. Although nerve-derived agrin has long been thought to play a key role during neuromuscular junction formation, the molecular mechanisms underlying its actions are only now coming into focus, following the recent discovery that agrin acts via the MuSK receptor tyrosine kinase.