Chromaffin cells of the adrenal medullary gland of mammals share properties both of endocrine and neuronal cells, and have been employed for many years as source of neurotransmitters and associated proteins. They also have been an important model for the study of many neurochemical and neurophysiological processes. These robust and easy to isolate cells have allowed neuroscientists to gain crucial information on the basic mechanisms involved in neurotransmitter synthesis and exocytosis, biogenesis of secretory vesicles, neuronal differentiation, among many other topics. A number of scientists (including several Nobel laureates) made classical discoveries including the catecholamine biosynthetic pathway, the stimulus-secretion coupling concept, the role of cytoskeleton in exocytosis, the first recording of elementary single-channel current and amperometry techniques to monitor single vesicle secretion. Nowadays, different groups around the world use these cells as a model to study ion channels, nicotinic and muscarinic receptors, proteins involved in calcium signalling, and of the exocytotic machinery, secretory vesicle recycling, neurotransmitter synthesis and storage, fine analysis of the exocytotic phenomenon at single event level, and the functional role of peptides resulting from chromogranins/secretogranins (that play key roles for biogenesis of dense core secretory vesicles) processing.