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 Ca2+-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.