Neuroendocrine cells release their secretion into the extracellular environment through calcium-dependent signalling pathways. These cells share common morphological and molecular features such as the expression of specific biomarkers, neurite outgrowth and dense core secretory granules. In order to elucidate the signalling pathways leading from undifferentiated to differentiated neuroendocrine cells, the role of voltage-dependent calcium channels, central actors in the excitation-secretion coupling, has been comprehensively investigated. T-type calcium channels appear to belong to the most important ion channel family involved in the neuroendocrine differentiation process. They could also participate in the development of neuroendocrine tumours.