The aqueous compartment inside a vesicle makes its first connection with the extracellular fluid through an intermediate structure termed the exocytotic fusion pore. Progress in exocytosis can be measured in terms of the formation and growth of the fusion pore. The fusion pore has become a major focus of research in exocytosis; sensitive biophysical measurements have provided various glimpses of what it looks like and how it behaves. Some of the principal questions about the molecular mechanism of exocytosis can be cast explicitly in terms of properties and transitions of fusion pores. This Review will present current knowledge about fusion pores in Ca(2+)-triggered exocytosis, highlight recent advances and relate questions about fusion pores to broader issues concerning how cells regulate exocytosis and how nerve terminals release neurotransmitter.