Pancreatic b-cells have an inherent ability to generate oscillatory signals that trigger insulin release. Coordination of the secretory activity among b-cells results in pulsatile insulin secretion from the pancreas, which is considered important for the action of the hormone in the target tissues. This lecture focuses on the mechanisms underlying oscillatory control of insulin secretion at the level of the individual b-cell. Ca²⁺ is the most important trigger of exocytosis and b-cell Ca²⁺ signalling has been extensively characterized. Recent studies have shown that glucose-induced oscillations of the cytoplasmic Ca²⁺ concentration are synchronized with oscillations in the cAMP concentration beneath the plasma membrane, where the nucleotide potently amplifies insulin exocytosis. The glucose- induced cAMP signals seem relatively independent of changes in the cytoplasmic Ca²⁺ concentration and are instead governed by variations in cell metabolism. Protein kinase A is required for proper induction of insulin secretion from glucose-stimulated cells, whereas the cAMP- dependence of maintained pulsatile secretion is mediated by the guanine nucleotide exchange factor Epac. Glucose-stimulated b-cells also show oscillations of phospholipase C activity and plasma membrane phosphoinositide lipid concentrations. In particular, phosphatidylinositol-3,4,5-trisphosphate show pronounced oscillations that reflect the kinetics of autocrine activation of insulin receptors. The functional effect of such insulin feedback remains unclear, but recent observations indicate that Zn2+ co-released with insulin contribute to amplitude and frequency regulation of pulsatile insulin secretion from glucose-stimulated b-cells.