Chemical synapses contain specialized pre- and postsynaptic structures that underlie rapid synaptic transmission and its modulation. Studies of postsynaptic organization have revealed a network of interacting proteins that enable rapid synaptic responses and their modulation. Recent genetic and electrophysiological studies on two active zone proteins-RIM and Munc13-reveal important roles in priming vesicles for Ca(2+)-triggered fusion and in mediating the regulation of this process. This work sheds new light on how presynaptic structure provides speed and plasticity to synaptic transmission.