Ca²⁺ influx through voltage-dependent Ca²⁺ channels plays a crucial role in stimulus-secretion coupling in pancreatic islet β-cells. Molecular and physiologic studies have identified multiple Ca²⁺ channel subtypes in rodent islets and insulin-secreting cell lines. The differential targeting of Ca²⁺ channel subtypes to the vicinity of the insulin secretory apparatus is likely to account for their selective coupling to glucose-dependent insulin secretion. In this article, I review these studies. In addition, I discuss temporal and spatial aspects of Ca²⁺ signaling in β-cells, the former involving the oscillatory activation of Ca²⁺ channels during glucose-induced electrical bursting, and the latter involving [Ca²⁺]_i elevation in restricted microscopic “domains”, as well as direct interactions between Ca²⁺ channels and secretory SNARE proteins. Finally, I review the evidence supporting a possible role for Ca²⁺ release from the endoplasmic reticulum in glucose-dependent insulin secretion, and evidence to support the existence of novel Ca²⁺ entry pathways. I also show that the β-cell has an elaborate and complex set of [Ca²⁺]_i signaling mechanisms that are capable of generating diverse and extremely precise [Ca²⁺]_i patterns. These signals, in turn, are exquisitely coupled in space and time to the β-cell secretory machinery to produce the precise minute-to-minute control of insulin secretion necessary for body energy homeostasis.