Easy access to rodent islets and insulinoma cells and the ease of measuring Ca²⁺ by fluorescent indicators have resulted in an overflow of data that have clarified minute details of Ca²⁺ signaling in the rodent islets. Our understanding of the mechanisms and the roles of Ca²⁺ signaling in the human islets, under physiological conditions, has been hugely influenced by uncritical extrapolation of the rodent data obtained under suboptimal experimental conditions. More recently, electrophysiological and Ca²⁺ studies have elucidated the ion channel repertoire relevant for Ca²⁺ signaling in the human islets and have examined their relative importance. Many new channels belonging to the transient receptor potential (TRP) family are present in the β-cells. Ryanodine receptors, nicotinic acid adenine dinucleotide phosphate channel, and Ca²⁺-induced Ca²⁺ release add new dimension to the complexity of Ca²⁺ signaling in the human β-cells. A lot more needs to be learnt about the roles of these new channels and CICR, not because that will be easy but because that will be difficult. Much de-learning will also be needed. Human β-cells do not have a resting state in the normal human body even under physiological fasting conditions. Their membrane potential under physiologically relevant resting conditions is ~−50 mV. Biphasic insulin secretion is an experimental epiphenomenon unrelated to the physiological pulsatile insulin secretion into the portal vein in the human body. Human islets show a wide variety of electrical activities and patterns of [Ca²⁺]_i changes, whose roles in mediating pulsatile secretion of insulin into the portal vein remain questionable. Future studies will hopefully be directed toward a better understanding of Ca²⁺ signaling in the human islets in the context of the pathogenesis and treatment of human diabetes.