Understanding how signaling molecules are released from cells is essential for furthering our knowledge of the basic biological mechanisms controlling many significant biological pathways. These molecules, including neurotransmitters, hormones, growth factors, and peptides, are released from cells via a process called exocytosis. Our laboratory has utilized a noninvasive method of measuring the release of oxidizable molecules from cells, known as carbon-fiber amperometry. In this chapter we will describe how we undertake such measurements, how the resulting data is analyzed, and what the outcomes mean in terms of physiology. We provide examples of our work measuring catecholamine release in single chromaffin cells as well as serotonin release from intact sections of colon.