Cyclic 3’5’AMP (cAMP) is an important physiological amplifier of glucose-induced insulin secretion by the pancreatic islet β-cell, where it is formed by the activity of adenylyl cyclases, which are stimulated by glucose, through elevation in intracellular calcium concentrations, and by the incretin hormones (GLP-1 and GIP). cAMP is rapidly degraded in the pancreatic islet β-cell by various cyclic nucleotide phosphodiesterase (PDE) enzymes. Many steps involved in glucose-induced insulin secretion are modulated by cAMP, which is also important in regulating pancreatic islet β-cell differentiation, growth and survival. This chapter discusses the formation, destruction and actions of cAMP in the islets with particular emphasis on the β-cell.